National recommendations for lung cancer screening for former and current smokers aged 55-80 years with a 30-pack-year smoking history create demand to implement efficient and effective systems to offer smoking cessation on a large scale. These older, high-risk smokers differ from participants in past clinical trials of behavioral and pharmacologic interventions for tobacco dependence. There is a gap in knowledge about how best to design systems to extend reach and treatments to maximize smoking cessation in the context of lung cancer screening. Eight clinical trials, seven funded by the National Cancer Institute and one by the Veterans Health Administration, address this gap and form the SCALE (Smoking Cessation within the Context of Lung Cancer Screening) collaboration. This paper describes methodological issues related to the design of these clinical trials: clinical workflow, participant eligibility criteria, screening indication (baseline or annual repeat screen), assessment content, interest in stopping smoking, and treatment delivery method and dose, all of which will affect tobacco treatment outcomes. Tobacco interventions consider the "teachable moment" offered by lung cancer screening, how to incorporate positive and negative screening results, and coordination of smoking cessation treatment with clinical events associated with lung cancer screening. Unique data elements, such as perceived risk of lung cancer and costs of tobacco treatment, are of interest. Lung cancer screening presents a new and promising opportunity to reduce morbidity and mortality resulting from lung cancer that can be amplified by effective smoking cessation treatment. SCALE teamwork and collaboration promise to maximize knowledge gained from the clinical trials.

Given the rapidly rising healthcare costs, it is important to understand the economic costs of hematopoietic cell transplantation (HCT), a procedure that is being used more frequently in the treatment of various hematologic disorders. Studies have reported a wide range of costs for HCT, from $36 000 to $88 000 (USD) for a single autologous transplantation for the initial hospitalization, to $200 000 (USD) or more for a myeloablative allogeneic procedure involving an unrelated donor. Common posttransplantation complications, such as infections and GVHD, have been shown to be significant cost drivers. Comparisons across studies are limited by differences in patient populations, cost ascertainment methods, and length of follow-up. This article summarizes the current state of knowledge about costs and cost-effectiveness of HCT, highlighting the challenges in conducting these studies and identifying important areas for future research. We discuss the need for more value-based assessments of HCT using high-quality approaches to measuring costs and outcomes so that potential future efforts to contain costs are well informed and appropriate.

Therapy-induced cellular senescence (TCS), characterized by prolonged cell cycle arrest, is an in vivo response of human cancers to chemotherapy and radiation. Unfortunately, TCS is reversible for a subset of senescent cells, leading to cellular reproliferation and ultimately tumor progression. This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer. We report the findings of a clinicopathological study in patients with locally advanced non-small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome. In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape, we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry. We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS. These polyploid senescent cells represent important transition states through which escape preferentially occurs. The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin-dependent kinase inhibitor family during TCS. Altogether, these studies underscore the importance of TCS in cancer therapeutics.The primary objective of anticancer therapy is the eradication of cancer cells by inducing cell death via apoptosis, autophagy and mitotic catastrophe. Complete eradication of most solid tumors such as non-small cell lung cancer (NSCLC) is rarely achieved using conventional treatment because of various biological and physiological limitations. These factors include the high frequency of p53 mutations, aberrant expression of antiapoptotic proteins such as Bcl-2 and survivin and various resistance mechanisms which impair tumor responses to cancer treatment. 1-3 Additionally, normal organ tolerance, drug bioavailability and tissue penetration further limit the efficacy of conventional chemotherapy and radiation in clinical settings.Telomere-independent therapy-induced cellular senescence (TCS), also known as stressed-induced premature senescence and accelerated cellular senescence, is increasingly recognized to be an important concept in cancer biology. The characteristic prolonged state of cell cycle arrest which defines senescence is elicited by sublethal doses of chemotherapy and ionizing radiation. 4,5 Over the past decade, TCS has been clearly demonstrated in a variety of cancer tissue culture models following abbreviated courses of antineoplastic drugs at subtumoricidal concentrations. 6 These studies consistently show that senescence response can be invoked by a wide spectrum of agents, which suggests that shared downstream pathways may be triggered by various cellular damage and stress signals. A particularly surprising finding is that despite expected dependency on key players of the cell damage and replicative

Broad adoption of lung cancer screening may inadvertently lead to negative population health outcomes if it is perceived as a substitute for smoking cessation.OBJECTIVE To understand views on smoking cessation from current smokers in the context of being offered lung cancer screening as a routine service in primary care. DESIGN, SETTING, AND PARTICIPANTSAs an ancillary study to the launch of a lung cancer screening program at 7 sites in the Veterans Health Administration, 45 in-depth semi-structured qualitative interviews about health beliefs related to smoking and lung cancer screening were administered from May 29 to September 22, 2014, by telephone to 37 current smokers offered lung cancer screening by their primary care physician. Analysis was conducted from June 15, 2014, to March 29, 2015. MAIN OUTCOMES AND MEASURESAttitudes and perceptions about the importance of smoking cessation in the context of lung cancer screening.RESULTS Lung cancer screening prompted most current smokers to reflect for the first time on what smoking means for their current and future health. However, 17 of 35 (49%) participants described mechanisms whereby screening lowered their motivation for cessation, including the perception that undergoing an imaging test yields the same health benefits as smoking cessation. Other misperceptions include the belief that everyone who participates in screening will benefit; the belief that screening and being able to return for additional screening offers protection from lung cancer; the perception by some individuals that findings from screenings have saved their lives by catching their cancer early when indeterminate findings are identified that can be monitored rather than immediately treated; and a reinforced belief in some individuals that a cancer-free screening test result indicates that they are among the lucky ones who will avoid the harms of smoking. CONCLUSIONS AND RELEVANCEIn this qualitative, lung cancer screening prompted many current smokers to reflect on their health and may serve as a potential opportunity to engage patients in discussions about smoking cessation. However, several concerning pathways were identified in which screening, when offered as part of routine care and described as having proven efficacy, may negatively influence smoking cessation. Health care professionals should be aware that the opportunity for early detection of lung cancer may be interpreted as a way of avoiding the harms of smoking. To promote cessation, discussions should focus on the emotional response to screening rather than clinical details (eg, nodule size) and address misperceptions about the value of early detection so that screening does not lower motivation to quit smoking.