Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists.

Chimeric antigen receptor (CAR) T-cell therapy is a recently approved breakthrough treatment that has become a new paradigm in treatment of recurrent or refractory B-cell lymphomas and pediatric or adult acute lymphoid leukemia. CAR T cells are a type of cellular immunotherapy that artificially enhances T cells to boost eradication of malignancy through activation of the native immune system. The CAR construct is a synthetically created functional cell receptor grafted onto previously harvested patient T cells, which bind to preselected tumor-associated antigens and thereby activate host immune signaling cascades to attack tumor cells. Advantages include a single treatment episode of 2-3 weeks and durable disease elimination, with remission rates of over 80%. Responses to therapy are more rapid than with conventional chemotherapy or immunotherapy, with intervening short-interval edema. CAR T-cell administration is associated with therapy-related toxic effects in a large percentage of patients, notably cytokine release syndrome, immune effect cell-associated neurotoxicity syndrome, and infections related to immunosuppression. Knowledge of the expected evolution of therapy response and potential adverse events in CAR T-cell therapy and correlation with the timeline of treatment are important to optimize patient care. Some toxic effects are radiologically evident, and familiarity with their imaging spectrum is key to avoiding misinterpretation. Other clinical toxic effects may be occult at imaging and are diagnosed on the basis of clinical assessment. Future directions for CAR T-cell therapy include new indications and expanded tumor targets, along with novel ways to capture T-cell activation with imaging. An invited commentary by Ramaiya and Smith is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Habitat Imaging Biomarkers for Diagnosis and Prognosis in Cancer Patients Infected with COVID-19.

OBJECTIVES: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population. METHODS: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and 420 CT scans from 414 cancer patients. In particular, the habitat imaging pipeline was developed to quantify the complex infection patterns by partitioning the whole lung regions into phenotypically different subregions. Subsequently, various machine learning models nested with feature selection were built for COVID-19 detection and severity prediction. RESULTS: These models showed almost perfect performance in COVID-19 infection diagnosis and predicting its severity during cross validation. Our analysis revealed that models built separately on the cancer population performed significantly better than those built on the general population and locked to test on the cancer population. This may be because of the significant difference among the habitat features across the two different cohorts. CONCLUSIONS: Taken together, our habitat imaging analysis as a proof-of-concept study has highlighted the unique radiologic features of cancer patients and demonstrated effectiveness of CT-based machine learning model in informing COVID-19 management in the cancer population.

Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naïve Extensive-Stage Small Cell Lung Cancer: A Phase 2 Randomized Study.

PURPOSE: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naïve, extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. RESULTS: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. CONCLUSIONS: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting.

Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: Radiotherapy might augment systemic antitumoral responses to immunotherapy. In the PEMBRO-RT (phase 2) and MDACC (phase 1/2) trials, patients with metastatic non-small-cell lung cancer were randomly allocated immunotherapy (pembrolizumab) with or without radiotherapy. When the trials were analysed individually, a potential benefit was noted in the combination treatment arm. However, owing to the small sample size of each trial, differences in response rates and outcomes were not statistically significant but remained clinically notable. We therefore did a pooled analysis to infer whether radiotherapy improves responses to immunotherapy in patients with metastatic non-small-cell lung cancer. METHODS: Inclusion criteria for the PEMBRO-RT and MDACC trials were patients (aged ≥18 years) with metastatic non-small-cell lung cancer and at least one unirradiated lesion to monitor for out-of-field response. In the PEMBRO-RT trial, patients had previously received chemotherapy, whereas in the MDACC trial, patients could be either previously treated or newly diagnosed. Patients in both trials were immunotherapy-naive. In the PEMBRO-RT trial, patients were randomly assigned (1:1) and stratified by smoking status (<10 vs ≥10 pack-years). In the MDACC trial, patients were entered into one of two cohorts based on radiotherapy schedule feasibility and randomly assigned (1:1). Because of the nature of the intervention in the combination treatment arm, blinding to radiotherapy was not feasible in either trial. Pembrolizumab was administered intravenously (200 mg every 3 weeks) with or without radiotherapy in both trials. In the PEMBRO-RT trial, the first dose of pembrolizumab was given sequentially less than 1 week after the last dose of radiotherapy (24 Gy in three fractions), whereas in the MDACC trial, pembrolizumab was given concurrently with the first dose of radiotherapy (50 Gy in four fractions or 45 Gy in 15 fractions). Only unirradiated lesions were measured for response. The endpoints for this pooled analysis were best out-of-field (abscopal) response rate (ARR), best abscopal disease control rate (ACR), ARR at 12 weeks, ACR at 12 weeks, progression-free survival, and overall survival. The intention-to-treat populations from both trials were included in analyses. The PEMBRO-RT trial (NCT02492568) and the MDACC trial (NCT02444741) are registered with ClinicalTrials.gov. FINDINGS: Overall, 148 patients were included in the pooled analysis, 76 of whom had been assigned pembrolizumab and 72 who had been assigned pembrolizumab plus radiotherapy. Median follow-up for all patients was 33 months (IQR 32·4-33·6). 124 (84%) of 148 patients had non-squamous histological features and 111 (75%) had previously received chemotherapy. Baseline variables did not differ between treatment groups, including PD-L1 status and metastatic disease volume. The most frequently irradiated sites were lung metastases (28 of 72 [39%]), intrathoracic lymph nodes (15 of 72 [21%]), and lung primary disease (12 of 72 [17%]). Best ARR was 19·7% (15 of 76) with pembrolizumab versus 41·7% (30 of 72) with pembrolizumab plus radiotherapy (odds ratio [OR] 2·96, 95% CI 1·42-6·20; p=0·0039), and best ACR was 43·4% (33 of 76) with pembrolizumab versus 65·3% (47 of 72) with pembrolizumab plus radiotherapy (2·51, 1·28-4·91; p=0·0071). Median progression-free survival was 4·4 months (IQR 2·9-5·9) with pembrolizumab alone versus 9·0 months (6·8-11·2) with pembrolizumab plus radiotherapy (hazard ratio [HR] 0·67, 95% CI 0·45-0·99; p=0·045), and median overall survival was 8·7 months (6·4-11·0) with pembrolizumab versus 19·2 months (14·6-23·8) with pembrolizumab plus radiotherapy (0·67, 0·54-0·84; p=0·0004). No new safety concerns were noted in the pooled analysis. INTERPRETATION: Adding radiotherapy to pembrolizumab immunotherapy significantly increased responses and outcomes in patients with metastatic non-small-cell lung cancer. These results warrant validation in a randomised phase 3 trial. FUNDING: Merck Sharp & Dohme.

Pembrolizumab with or without radiation therapy for metastatic non-small cell lung cancer: a randomized phase I/II trial.

BACKGROUND: In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung and liver lesions from metastatic non-small cell lung cancer (mNSCLC). METHODS: Patients with lung or liver lesions amenable to RT plus at least one additional non-contiguous lesion were included regardless of programmed death-ligand 1 (PD-L1) status. Pembrolizumab was given at 200 mg every 3 weeks for up to 32 cycles with or without concurrent RT. Metastatic lesions were treated with stereotactic body RT (SBRT; 50 Gy in 4 fractions) if clinically feasible or with traditionally fractionated RT (45 Gy in 15 fractions) if not. The primary end point was the best out-of-field lesion response, and a key secondary end point was progression-free survival (PFS). RESULTS: The median follow-up time was 20.4 months. One hundred patients (20 phase I, 80 phase II) were evaluable for toxicity, and 72 phase II patients were evaluable for treatment response. No patients in the phase I group experienced grade 4-5 events; in the phase II group, two had grade 4 events and nine had grade 3 events. The ORR in the combined-modality cohort (irrespective of RT schema) was 22%, vs 25% in the pembrolizumab group (irrespective of receipt of salvage RT) (p=0.99). In the concurrent pembrolizumab+RT groups, the out-of-field ORRs were 38% in the pembrolizumab+SBRT group and 10% in the pembrolizumab+traditional RT group. When examining the pembrolizumab-alone patients, the out-of-field ORRs were 33% in those designated to receive salvage SBRT (if required) and 17% for salvage traditional RT. In all patients, the median PFS for pembrolizumab alone was 5.1 months (95% CI 3.4 to 12.7 months), and pembrolizumab/RT (regardless of schema) was 9.1 months (95% CI 3.6 to 18.4 months) (p=0.52). An exploratory analysis revealed that for patients with low PD-L1 expression, the median PFS was 4.6 vs 20.8 months for pembrolizumab with and without RT, respectively (p=0.004). CONCLUSIONS: Concurrent immunoradiotherapy for mNSCLC is safe, although larger trials are required to address which patients benefit most from RT. TRIAL REGISTRATION NUMBER: NCT02444741.

ACR Appropriateness Criteria® Occupational Lung Diseases.

Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients.

The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease: Outcomes, Toxicities, and Low-Dose Radiation-Related Abscopal Responses.

Ipilimumab is effective for patients with melanoma, but not for those with less immunogenic tumors. We report a phase II trial of ipilimumab with concurrent or sequential stereotactic ablative radiotherapy to metastatic lesions in the liver or lung (NCT02239900). Ipilimumab (every 3 weeks for 4 doses) was given with radiotherapy begun during the first dose (concurrent) or 1 week after the second dose (sequential) and delivered as 50 Gy in 4 fractions or 60 Gy in 10 fractions to metastatic liver or lung lesions. In total, 106 patients received ≥1 cycle of ipilimumab with radiation. Median follow-up was 10.5 months. Median progression-free survival time was 2.9 months (95% confidence interval, 2.45-3.40), and median overall survival time was not reached. Rates of clinical benefit of nonirradiated tumor volume were 26% overall, 28% for sequential versus 20% for concurrent therapy (P = 0.250), and 31% for lung versus 14% for liver metastases (P = 0.061). The sequential lung group had the highest rate of clinical benefit at 42%. There were no differences in treatment-related adverse events between groups. Exploratory analysis of nontargeted lesions revealed that lesions receiving low-dose radiation were more likely to respond than those that received no radiation (31% vs. 5%, P = 0.0091). This phase II trial of ipilimumab with stereotactic radiotherapy describes satisfactory outcomes and low toxicities, lending support to further investigation of combined-modality therapy for metastatic cancers.

Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy.

BACKGROUND: Preclinical evidence suggests that low-dose radiation may overcome the inhibitory effects of the tumor stroma and improve a tumor's response to immunotherapy, when combined with high-dose radiation to another tumor. The aim of this study was to evaluate tumor responses to this combination in a clinical setting. METHODS: A post-hoc analysis of 3 ongoing immunoradiation trials was performed. Twenty-six (of 155) patients received low-dose radiation (1-20 Gy total), either as scatter from high-dose radiation or from intentional treatment of a second isocenter with low-dose radiation, were evaluated for response. The low-dose lesions were compared to lesions that received no radiation (< 1 Gy total). Response rates, both defined as complete and partial responses as defined by RECIST criteria were used to compare lesion types. RESULTS: The 26 patients had a total of 83 lesions for comparison (38 receiving low-dose, 45 receiving no-dose). The average dose given to low-dose lesions was 7.3 Gy (1.1-19.4 Gy), and the average time to response was 56 days. Twenty-two out of 38 (58%) low-dose lesions met the PR/CR criteria for RECIST compared with 8 out of 45 (18%) no-dose lesions (P = 0.0001). The median change for longest diameter size for low-dose lesions was - 38.5% compared to 8% in no-dose lesions (P < 0.0001). Among the low-dose lesions that had at least one no-dose lesion within the same patient as a control (33 and 45 lesions respectively), 12 low-dose lesions (36%) responded without a corresponding response in their no-dose lesions; Conversely, two (4%) of the no-dose lesions responded without a corresponding response in their low-dose lesion (P = 0.0004). CONCLUSIONS: Low-dose radiation may increase systemic response rates of metastatic disease treated with high-dose radiation and immunotherapy.

ACR Appropriateness Criteria® Noninvasive Clinical Staging of Primary Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths in both men and women. The major risk factor for lung cancer is personal tobacco smoking, particularly for small-cell lung cancer (SCLC) and squamous cell lung cancers, but other significant risk factors include exposure to secondhand smoke, environmental radon, occupational exposures, and air pollution. Education and socioeconomic status affect both incidence and outcomes. Non-small-cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, comprises about 85% of lung cancers. SCLC accounts for approximately 13% to 15% of cases. Prognosis is directly related to stage at presentation. NSCLC is staged using the eighth edition of the tumor-node-metastasis (TNM) criteria of the American Joint Committee on Cancer. For SCLC the eighth edition of TNM staging is recommended to be used in conjunction with the modified Veterans Administration Lung Study Group classification system distinguishing limited stage from extensive stage SCLC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Fibrosing/Sclerosing Lesions of the Mediastinum: A Review.

Fibrosing lesions of the mediastinum represent a small but challenging group of lesions that range in etiology from infectious to idiopathic to neoplastic. The diagnosis of such lesions becomes more challenging in the setting of mediastinoscopic biopsies. In addition, over the years, there has been further accumulation of knowledge of the clinical aspects of these lesions that needs to be incorporated into their evaluation. Therefore, it is essential that in the general evaluation of these fibrosing processes, one not only carefully examines the histopathologic features of the lesion, that of a fibroinflammatory process with the appropriate histochemical and immunohistochemical studies, but also carefully evaluates the clinical presentation and imaging findings. Needless to say, as will be illustrated in this review, determining a definitive unequivocal diagnosis on a small mediastinoscopic biopsy may be difficult, and often one needs to provide guidance on the perspective of the histologic features present. In some cases, mainly tumoral conditions with extensive fibrosis, a conclusive diagnosis can be made; however, it is those cases in which the extensive fibrosis is the only histopathologic feature where more appropriate guidance is required. While this review will focus more on the non-neoplastic fibroinflammatory lesions of the mediastinum, within the discussion of differential diagnoses, we will discuss some neoplastic conditions that commonly show extensive fibrosing features.

ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompetent Patients.

Acute respiratory illness, defined as cough, sputum production, chest pain, and/or dyspnea (with or without fever), is a major public health issue, accounting for millions of doctor office and emergency department visits every year. While most cases are due to self-limited viral infections, a significant number of cases are due to more serious respiratory infections where delay in diagnosis can lead to morbidity and mortality. Imaging plays a key role in the initial diagnosis and management of acute respiratory illness. This study reviews the current literature concerning the appropriate role of imaging in the diagnosis and management of the immunocompetent adult patient initially presenting with acute respiratory illness. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Chronic Dyspnea-Noncardiovascular Origin.

Chronic dyspnea may result from a variety of disorders of cardiovascular, pulmonary, gastrointestinal, neuromuscular, systemic, and psychogenic etiology. This article discusses guidelines for the initial imaging of six variants for chronic dyspnea of noncardiovascular origin: (1) Chronic dyspnea of unclear etiology; (2) Chronic dyspnea with suspected chronic obstructive pulmonary disease; (3) Chronic dyspnea with suspected central airways disease; (4) Chronic dyspnea with suspected interstitial lung disease; (5) Chronic dyspnea with suspected disease of the pleura or chest wall; and (6) Chronic dyspnea with suspected diaphragm dysfunction. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The epidemiology of lung cancer.

The incidence and mortality from lung cancer is decreasing in the US due to decades of public education and tobacco control policies, but are increasing elsewhere in the world related to the commencement of the tobacco epidemic in various countries and populations in the developing world. Individual cigarette smoking is by far the most common risk factor for lung carcinoma; other risks include passive smoke inhalation, residential radon, occupational exposures, infection and genetic susceptibility. The predominant disease burden currently falls on minority populations and socioeconomically disadvantaged people. In the US, the recent legalization of marijuana for recreational use in many states and the rapid growth of commercially available electronic nicotine delivery systems (ENDS) present challenges to public health for which little short term and no long term safety data is available.

Role of Dual-Energy Computed Tomography in Thoracic Oncology.

Dual-energy CT (DECT) is an emerging technology that has potential to enhance diagnostic performance and radiologists' confidence in the evaluation of thoracic malignancies. DECT clinical applications include characterization of solitary pulmonary nodule, lung masses and mediastinal tumors. DECT-derived iodine uptake quantification may assist in characterization of tumor differentiation and gene expression. The use DECT in oncology has potential to improve lung cancer staging, therapy planning, and assessment of response to therapy as well as detection of incidental pulmonary embolism.

Implications for high-precision dose radiation therapy planning or limited surgical resection after percutaneous computed tomography-guided lung nodule biopsy using a tract sealant.

PURPOSE: Precision radiation therapy such as stereotactic body radiation therapy and limited resection are being used more frequently to treat intrathoracic malignancies. Effective local control requires precise radiation target delineation or complete resection. Lung biopsy tracts (LBT) on computed tomography (CT) scans after the use of tract sealants can mimic malignant tract seeding (MTS) and it is unclear whether these LBTs should be included in the calculated tumor volume or resected. This study evaluates the incidence, appearance, evolution, and malignant seeding of LBTs. METHODS AND MATERIALS: A total of 406 lung biopsies were performed in oncology patients using a tract sealant over 19 months. Of these patients, 326 had follow-up CT scans and were included in the study group. Four thoracic radiologists retrospectively analyzed the imaging, and a pathologist examined 10 resected LBTs. RESULTS: A total of 234 of 326 biopsies (72%, including primary lung cancer [n = 98]; metastases [n = 81]; benign [n = 50]; and nondiagnostic [n = 5]) showed an LBT on CT. LBTs were identified on imaging 0 to 3 months after biopsy. LBTs were typically straight or serpiginous with a thickness of 2 to 5 mm. Most LBTs were unchanged (92%) or decreased (6.3%) over time. An increase in LBT thickness/nodularity that was suspicious for MTS occurred in 4 of 234 biopsies (1.7%). MTS only occurred after biopsy of metastases from extrathoracic malignancies, and none occurred in patients with lung cancer. CONCLUSIONS: LBTs are common on CT after lung biopsy using a tract sealant. MTS is uncommon and only occurred in patients with extrathoracic malignancies. No MTS was found in patients with primary lung cancer. Accordingly, potential alteration in planned therapy should be considered only in patients with LBTs and extrathoracic malignancies being considered for stereotactic body radiation therapy or wedge resection.

Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer.

Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m2/day, days 1 to 5, of a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent. Response was determined by imaging at weeks 4 and 8, and every 8 weeks thereafter. Improvement in PFS at 4 months was the primary end point. Secondary objectives included overall response rate (ORR), overall survival (OS), and safety and tolerability of veliparib with TMZ. Exploratory objectives included PARP-1 and SLFN11 immunohistochemical expression, MGMT promoter methylation, and circulating tumor cell quantification. Results No significant difference in 4-month PFS was noted between TMZ/veliparib (36%) and TMZ/placebo (27%; P = .19); median OS was also not improved significantly with TMZ/veliparib (8.2 months; 95% CI, 6.4 to 12.2 months; v 7.0 months; 95% CI, 5.3 to 9.5 months; P = .50). However, ORR was significantly higher in patients receiving TMZ/veliparib compared with TMZ/placebo (39% v 14%; P = .016). Grade 3/4 thrombocytopenia and neutropenia more commonly occurred with TMZ/veliparib: 50% versus 9% and 31% versus 7%, respectively. Significantly prolonged PFS (5.7 v 3.6 months; P = .009) and OS (12.2 v 7.5 months; P = .014) were observed in patients with SLFN11-positive tumors treated with TMZ/veliparib. Conclusion Four-month PFS and median OS did not differ between the two arms, whereas a significant improvement in ORR was observed with TMZ/veliparib. SLFN11 expression was associated with improved PFS and OS in patients receiving TMZ/veliparib, suggesting a promising biomarker of PARP-inhibitor sensitivity in SCLC.

Postoperative Imaging and Complications in Resection of Lung Cancer.

Surgical resection offers the best hope of cure for patients with operable early-stage lung cancer. Wedge resection, segmentectomy, lobectomy, or pneumonectomy may be performed depending on the size and location of the tumor. Radiologists must be familiar with the types of surgical resection utilized in the treatment of lung carcinoma and with their normal and abnormal postsurgical appearance on imaging studies. Prompt identification of postoperative complications on imaging is essential to appropriate patient management and helps to determine when additional intervention is warranted.

Imaging on Lung Cancer and Treatment with Targeted Therapy.

The identification of genetic mutations known as oncogenic driver mutations that lead to the growth and survival of cancer cells has been an important advance in the field of oncology. Treatment in advanced non-small-cell lung cancer (NSCLC) has transitioned from a more general approach to a more personalized approach based on genetic mutations of the cancer itself. Common mutations detected in patients with advanced NSCLC include mutations of epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). Targeted therapies are aimed at the products of these gene mutations and include erlotinib (used in epidermal growth factor receptor mutant NSCLC) and crizotinib (used in anaplastic lymphoma kinase positive NSCLC). In this review, we discuss common genetic mutations in advanced NSCLC, the role of targeted therapies, and imaging findings that can be associated with various genetic mutations.