Purpose A phase I study was conducted to determine safety, clinical efficacy, and anti-tumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral (IT) administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222). Experimental Design Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 × 106, 5 × 106, 1 × 107, or 3 × 107 dendritic cells/injection) by CT- or bronchoscopic-guided IT injections (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFN-γ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by immunohistochemistry (IHC) and for PD-L1 expression by IHC and real-time PCR (RT-PCR). Results Twenty-five percent (4/16) of patients had stable disease at day 56. Median survival was 3.9 months. ELISPOT assays revealed 6 of 16 patients had systemic responses against tumor associated antigens (TAA). Tumor CD8+ T cell infiltration was induced in 54% of subjects (7/13; 3.4-fold average increase in the number of CD8+ T cells per mm2). Patients with increased CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA expression. Conclusions Intratumoral vaccination with Ad-CCL21-DC resulted in 1) induction of systemic tumor antigen-specific immune responses, 2) enhanced tumor CD8+ T cell infiltration, and 3) increased tumor PD-L1 expression. Future studies will evaluate the role of combination therapies with PD-1/PD-L1 checkpoint inhibition combined with DC-CCL21 in situ vaccination.

The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imagingbased screening to reduce the burden of lung cancer are discussed.

Cryoablation is a safe and effective treatment for pulmonary metastases with preserved quality of life following intervention.

Radiofrequency ablation (RFA) is used to treat pulmonary malignancies. Although preliminary results are suggestive of a survival benefit, local progression rates are appreciable. Because a patient can undergo repeat treatment if recurrence is detected early, reliable post-RFA imaging follow-up is critical. The purpose of this article is to describe (a) an algorithm for post-RFA imaging surveillance; (b) the computed tomographic (CT) appearance, size, enhancement, and positron emission tomographic (PET) metabolic activity of the ablation zone; and (c) CT, PET, and dual-modality imaging with PET and CT (PET/CT) features suggestive of partial ablation or tumor recurrence and progression. CT is routinely used for post-RFA follow-up. PET and PET/CT have emerged as auxiliary follow-up techniques. CT with nodule densitometry may be used to supplement standard CT. Post-RFA follow-up was divided into three phases: early (immediately after to 1 week after RFA), intermediate (>1 week to 2 months), and late (>2 months). CT and PET imaging features suggestive of residual or recurrent disease include (a) increasing contrast material uptake in the ablation zone (>180 seconds on dynamic images), nodular enhancement measuring more than 10 mm, any central enhancement greater than 15 HU, and enhancement greater than baseline anytime after ablation; (b) growth of the RFA zone after 3 months (compared with baseline) and definitely after 6 months, peripheral nodular growth and change from ground-glass opacity to solid opacity, regional or distant lymph node enlargement, and new intrathoracic or extrathoracic disease; and (c) increased metabolic activity beyond 2 months, residual activity centrally or at the ablated tumor, and development of nodular activity.

QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.