Characterization of continuous bed motion effects on patient breathing and respiratory motion correction in PET/CT imaging.

Continuous bed motion (CBM) was recently introduced as an alternative to step-and-shoot (SS) mode for PET/CT data acquisition. In CBM, the patient is continuously advanced into the scanner at a preset speed, whereas in SS, the patient is imaged in overlapping bed positions. Previous investigations have shown that patients preferred CBM over SS for PET data acquisition. In this study, we investigated the effect of CBM versus SS on patient breathing and respiratory motion correction. One hundred patients referred for PET/CT were scanned using a Siemens mCT scanner. Patient respiratory waveforms were recorded using an Anzai system and analyzed using four methods: Methods 1 and 2 measured the coefficient of variation (COV) of the respiratory cycle duration (RCD) and amplitude (RCA). Method 3 measured the respiratory frequency signal prominence (RSP) and method 4 measured the width of the HDChest optimal gate (OG) window when using a 35% duty cycle. Waveform analysis was performed over the abdominothoracic region which exhibited the greatest respiratory motion and the results were compared between CBM and SS. Respiratory motion correction was assessed by comparing the ratios of SUVmax, SUVpeak, and CNR of focal FDG uptake, as well as Radiologists' visual assessment of corresponding image quality of motion corrected and uncorrected images for both acquisition modes. The respiratory waveforms analysis showed that the RCD and RCA COV were 3.7% and 33.3% lower for CBM compared to SS, respectively, while the RSP and OG were 30.5% and 2.0% higher, respectively. Image analysis on the other hand showed that SUVmax, SUVpeak, and CNR were 8.5%, 4.5%, and 3.4% higher for SS compared to CBM, respectively, while the Radiologists' visual comparison showed similar image quality between acquisition modes. However, none of the results showed statistically significant differences between SS and CBM, suggesting that motion correction is not impacted by acquisition mode.

Revisions to the TNM Staging of Lung Cancer: Rationale, Significance, and Clinical Application.

Lung cancer remains the leading cause of cancer-related mortality worldwide. To formulate effective treatment strategies and optimize patient outcomes, accurate staging is essential. Lung cancer staging has traditionally relied on a TNM staging system, for which the International Association for the Study of Lung Cancer (IASLC) has recently proposed changes. The revised classification for this eighth edition of the TNM staging system (TNM-8) is based on detailed analysis of a new large international database of lung cancer cases assembled by the IASLC for the purposes of this project. Fundamental changes incorporated into TNM-8 include (a) modifications to the T classification on the basis of 1-cm increments in tumor size; (b) grouping of lung cancers that result in partial or complete lung atelectasis or pneumonitis; (c) grouping of tumors with involvement of a main bronchus irrespective of distance from the carina; (d) reassignment of diaphragmatic invasion in terms of T classification; (e) elimination of mediastinal pleural invasion from the T classification; and (f) subdivision of the M classification into different descriptors on the basis of the number and site of extrathoracic metastases. In response to these revisions, established stage groups have been modified, and others have been created. In addition, recommendations for classifying patterns of disease that result in multiple sites of pulmonary involvement, including multiple primary lung cancers, lung cancers with separate tumor nodules, multiple ground-glass/lepidic lesions, and consolidation, as well as recommendations for lesion measurement, are addressed. Understanding the key revisions introduced in TNM-8 allows radiologists to accurately stage patients with lung cancer and optimize therapy. ©RSNA, 2018.

A phase I/II study combining erlotinib and dasatinib for non-small cell lung cancer.

BACKGROUND: EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC. METHODS: The phase I 3+3 dose-escalation study enrolled patients with solid tumors to determine the MTD. The phase II trial enrolled patients with advanced NSCLC who had undergone no previous treatments to determine progression-free survival (PFS) and response. Pharmacokinetic and tissue biomarker analyses were performed. RESULTS: MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion. No responses were observed in phase I. The 35 NSCLC patients treated in phase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. Median PFS was 3.3 months. Epithelial-mesenchymal transition markers did not correlate with outcomes. CONCLUSION: The combination of erlotinib and dasatinib is safe and feasible in NSCLC. The results of this study do not support use of this combination in molecularly unselected NSCLC.

Small cell lung carcinoma: staging, imaging, and treatment considerations.

Small cell lung carcinoma (SCLC) is the most common primary pulmonary neuroendocrine malignancy and is characterized by a rapid doubling time and high growth fraction. Approximately 60%-70% of patients present with metastatic disease at the time of diagnosis, and their prognosis is poor. However, improved survival has been demonstrated when SCLC is diagnosed early and specific treatment strategies are used. A modified version of the Veterans Administration Lung Cancer Study Group (VALSG) staging system has traditionally been used to categorize SCLC as limited-stage or extensive-stage disease to guide therapy. However, the International Association for the Study of Lung Cancer has recommended that the current seventh edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for lung cancer replace the VALSG system for staging of SCLC. Appropriate staging and patient management require knowledge of imaging manifestations of SCLC across multiple imaging modalities, the strengths and weaknesses of specific examinations, the correlation of these findings with the staging criteria used in clinical practice, and the impact of appropriate staging on patient treatment and survival. Computed tomography (CT) is primarily used to evaluate the primary tumor and the extent of intrathoracic disease. In recent years, however, 2-[fluorine-18]fluoro-2-deoxy-d-glucose positron emission tomography/CT has proved to be more accurate than conventional imaging in the staging of SCLC and can be used to guide therapy and assess treatment response.

Update in the evaluation of the solitary pulmonary nodule.

A solitary pulmonary nodule (SPN) is defined as a round opacity that is smaller than 3 cm. It may be solid or subsolid in attenuation. Semisolid nodules may have purely ground-glass attenuation or be partly solid (mixed solid and ground-glass attenuation). The widespread use of multidetector computed tomography (CT) has increased the detection of SPNs. Although clinical assessment of patients' risk factors for malignancy--such as age, smoking history, and history of malignancy--is important to determine appropriate treatment, in the recently published Fleischner guidelines for subsolid nodules, smoking history does not factor into their recommendations for management because there is an increasing incidence of lung adenocarcinoma in younger and nonsmoking patients. At imaging evaluation, obtaining prior chest radiographs or CT images is useful to assess nodule growth. Further imaging evaluation, including CT enhancement studies and positron emission tomography (PET), helps determine the malignant potential of solid SPNs. For subsolid nodules, initial follow-up CT is performed at 3 months to determine persistence, because lesions with an infectious or inflammatory cause can resolve in the interval. CT enhancement studies are not applicable for subsolid nodules, and PET is of limited utility because of the low metabolic activity of these lesions. Because of the likelihood that persistent subsolid nodules represent adenocarcinoma with indolent growth, serial imaging reassessment for a minimum of 3 years and/or obtaining tissue samples for histologic analysis are recommended. In the follow-up of subsolid SPNs, imaging features that indicate an increased risk for malignancy include an increase in size, an increase in attenuation, and development of a solid component.

Multidetector CT evaluation of airway stents: what the radiologist should know.

Airway stents are increasingly used to treat symptomatic patients with obstructive tracheobronchial diseases who are not amenable to surgical resection or who have poor performance status, precluding them from resection. The most common conditions that are treated with tracheobronchial stents are primary lung cancer and metastatic disease. However, stents have also been used to treat patients with airway stenosis related to a variety of benign conditions, such as tracheobronchomalacia, relapsing polychondritis, postintubation tracheal stenosis, postoperative anastomotic stenosis, and granulomatous diseases. Additionally, airway stents can be used as a barrier method in the management of esophagorespiratory fistulas. Many types of stents are available from different manufacturers. Principally, they are classified as silicone; covered and uncovered metal; or hybrid, which are made of silicone and reinforced by metal rings. The advantages and disadvantages of each type of airway stent are carefully considered when choosing the most appropriate stent for each patient. Multidetector computed tomography plays an important role in determining the cause and assessing the location and extent of airway obstruction. Moreover, it is very accurate in its depiction of complications after airway stent placement.

PET-CT: current applications and new developments in the thorax.

Positron emission tomography computed tomography(PET-CT) imaging has emerged as an essential clinical diagnostic tool in the evaluation of thoracic abnormalities. Currently, its primary role is for tumor imaging; it helps to differentiate benign from malignant nodules, stage tumors, determine response, and follow patients after therapy is complete. It has also been used for nononcologic diseases, but the indications are less well defined. PET is a fundamental component of the molecular imaging initiative, and as new more specific imaging probes and better instrumentation are developed, PET-CT is certain to improve diagnostic accuracy and become even more integrated into the imaging armamentarium.

The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: This study analyzed all metastatic categories of the current TNM classification of NSCLC to propose modifications of the M component in the next edition (ninth) of the classification. METHODS: A database of 124,581 patients diagnosed between 2011 and 2019 was established; of these, 14,937 with NSCLC in stages IVA to IVB were available for this analysis. Overall survival was calculated using the Kaplan-Meier method, and prognosis was assessed using multivariable-adjusted Cox proportional hazards regression. RESULTS: The eighth edition M categories revealed good discrimination in the ninth edition data set. Assessments revealed that an increasing number of metastatic lesions were associated with decreasing prognosis; because this seems to be a continuum and adjustment for confounders was not possible, no specific lesion number was deemed appropriate for stage classification. Among tumors involving multiple metastases, decreasing prognosis was found with an increasing number of organ systems involved. Multiple assessments, including after adjustment for potential confounders, revealed that M1c patients who had metastases to a single extrathoracic organ system were prognostically distinct from M1c patients who had involvement of multiple extrathoracic organ systems. CONCLUSIONS: These data validate the eighth edition M1a and M1b categories, which are recommended to be maintained. We propose the M1c category be divided into M1c1 (involvement of a single extrathoracic organ system) and M1c2 (involvement of multiple extrathoracic organ systems).

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

SABR for Sarcoma Lung Metastases: Indications for Treatment and Guidance for Patient Selection.

PURPOSE: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases. METHODS AND MATERIALS: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: We identified 70 patients with soft tissue sarcoma treated with SABR to 98 metastatic lung lesions. Local recurrence-free survival after SABR treatment was 83% at 2 years. On univariable analysis, receipt of comprehensive SABR to all sites of pulmonary metastatic disease at the time of treatment was associated with improved progression-free survival (PFS; hazard ratio [HR], 0.51 [0.29-0.88]; P = .02). On multivariable analysis, only having systemic disease controlled at the time of SABR predicted improved PFS (median PFS, 14 vs 4 months; HR, 0.37 [0.20-0.69]; P = .002) and overall survival (median overall survival, 51 vs 14 months; HR, 0.17 [0.08-0.35]; P < .0001). CONCLUSIONS: SABR provides durable long-term local control for sarcoma lung metastases. The most important predictor for improved outcomes was systemic disease control. Careful consideration of these factors should help guide decisions in a multidisciplinary setting to appropriately select the optimal candidates for SABR.

The influence of histopathologic tumor viability on long-term survival and recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma.

OBJECTIVE: Our aim was to validate the effect of histopathologic tumor viability (HTV) on extended survival outcomes and assess the prognostic ability of the current staging system in patients receiving preoperative chemoradiotherapy (CRT). BACKGROUND: The American Joint Committee on Cancer, 7th Edition, esophageal carcinoma staging system is derived from patients treated with surgery alone and does not account for the treatment effect of CRT. The extent of HTV after CRT is based on response to neoadjuvant therapy and has been shown to correlate with patient outcome. METHODS: Medical records of 1278 patients who underwent esophagectomy (1990-2011) were reviewed; 784 patients underwent preoperative CRT. Histologic tumor viability was assessed in 602 patients and classified as 0% to 10%, 11% to 50%, and more than 50%. Survival was estimated using the Kaplan-Meier method at potential median follow-up of 67 months. Univariate and multivariate analyses identified variables associated with survival. RESULTS: Multivariate analysis identified HTV of greater than 50% (P < 0.001, HR 2.5), positive pathologic nodal status (P < 0.001, HR 1.6), and positive clinical nodal status (P = 0.002, HR 1.5) but not pathologic T status (P = 0.816, HR 1.2) to be independently associated with survival. Actuarial 5- and 10-year survival was 52% and 43% (HTV of 0%-10%), 45% and 33% (HTV of 11%-50%), and 16% for both (HTV of >50%). The best 5-year survival 56% was achieved in N0 patients with HTV of 0% to 10% (P = 0.056, HR 1.0), contrary to 6% observed in node-positive patients with HTV of greater than 50% (P < 0.001, HR 3.1). Patients with HTV of greater than 50% demonstrated distant recurrence more frequently than those with HTV of less than 50% (51% vs 33%, P = 0.010, OR: 2.2) CONCLUSIONS:: After preoperative chemoradiation, long-term outcomes of esophageal carcinoma are best predicted utilizing histologic tumor viability; HTV may be a practical early endpoint predicting efficacy of therapy.

Multimodality imaging evaluation of esophageal cancer: staging, therapy assessment, and complications.

Esophageal cancer is among the leading causes of cancer-related deaths worldwide. The management of patients with esophageal cancer is determined to a large extent by patient performance status, location of the primary cancer, and stage of disease at presentation. Multimodality regimens combining neoadjuvant chemotherapy and/or radiotherapy followed by surgery have been increasingly used in suitable candidates with locally advanced cancer. There is substantial morbidity and mortality associated with this treatment strategy, which makes appropriate patient selection important. Endoscopic esophageal ultrasound is the optimal modality to evaluate the local extent of the primary tumor and diagnose locoregional nodal metastasis. Computed tomography is more useful in detecting distant nodal and systemic metastasis. Positron emission tomography/CT is increasingly being used in patient management and improves the accuracy of staging, particularly in the detection of distant nodal and systemic metastatic disease. In this article, we review the role of imaging in the staging, assessment of therapeutic response, and detection of recurrent disease, as well as the evaluation of therapeutic complications in patients with esophageal cancer.

Liver Injury in Patients With Distal Esophageal Carcinoma After Precision Radiation Therapy: Systematic Review of FDG-PET/CT Patterns.

OBJECTIVE: To determine the incidence and various patterns of radiation-induced liver injury (RILI) and its temporal evolution on fluorodeoxiglucose-positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemoradiation using precision radiation in patients with esophageal carcinoma. MATERIAL AND METHODS: We evaluated 639 patients with locally advanced esophageal carcinoma who had serial FDG-PET/CTs after neoadjuvant chemoradiation. Two readers reviewed the imaging studies in consensus and recorded the cases where new foci of increased FDG uptake were identified within the radiated liver parenchyma. RILI was confirmed by follow-up imaging or percutaneous biopsy. RESULTS: FDG-avid RILI developed in 39/639 (6%) of patients. The caudate and left hepatic lobe were involved in all cases. There were various patterns of increased FDG uptake: 38% of patients had a single focus of increased FDG uptake and 62% had 2 regions of increased FDG uptake, which were focal nodular or diffuse or a combination of focal nodular and diffuse FDG uptake. On CT, 72% of patients had a poorly-marginated region of low attenuation and 28% had a well-defined region of low attenuation with sharp, well-defined linear borders in the location of the radiation, as confirmed by the treatment plan. CONCLUSION: The caudate and left hepatic lobes were involved in all cases of RILI. The various imaging patterns of RILI on FDG-PET/CT include 1 or 2 regions of increased FDG uptake with a nodular, diffuse, or combined appearance. Awareness of this potential complication of radiation therapy and knowledge of the imaging manifestations of RILI is important to avoid misinterpretation as a metastasis.

Considerations for Imaging of Malignant Pleural Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group.

Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleura that presents unique radiologic challenges with regard to accurate and reproducible assessment of disease extent at staging and follow-up imaging. By optimizing and harmonizing technical approaches to imaging MPM, the best quality imaging can be achieved for individual patient care, clinical trials, and imaging research. This consensus statement represents agreement on harmonized, standard practices for routine multimodality imaging of MPM, including radiography, computed tomography, 18F-2-deoxy-D-glucose positron emission tomography, and magnetic resonance imaging, by an international panel of experts in the field of pleural imaging assembled by the International Mesothelioma Interest Group. In addition, modality-specific technical considerations and future directions are discussed. A bulleted summary of all technical recommendations is provided.

Nomograms for prognostication of outcome in patients with esophageal and gastroesophageal carcinoma undergoing definitive chemoradiotherapy.

INTRODUCTION: Level-1 evidence for definitive chemoradiotherapy (bimodality therapy or BM therapy) has been established for patients with esophageal and gastroesophageal junction cancers (EGEJC) who otherwise do not qualify for surgery; however, tools to estimate individual patient prognosis are unavailable. We used a number of clinical pre- and post-treatment parameters to establish two nomograms: for overall survival (OS) and relapse-free survival (RFS). METHODS: From 2002 through 2010, 257 consecutive patients with EGEJC who received BM therapy and had pre- and post-treatment positron emission tomography (PET) and post-treatment endoscopic biopsies among other assessments were analyzed from a prospectively maintained database. Standard statistical methods were used to generate the nomograms. RESULTS: None of the 257 patients underwent surgery. Persistent or recurrent cancer was documented in 187 (72.8%) patients. The estimated median survival duration for all 257 patients was 21.1 months (95% CI, 18.9-27.1) and the median RFS duration was 11.6 months (95% CI, 9.43-15.0). After BM therapy, 155 (60.3%) patients achieved a clinical complete response (cCR). In multivariate analyses, maximum initial standardized uptake value and cCR were independent prognostic variables for OS (p = 0.038, p < 0.001). Nomogram concordance indices of 0.70 for OS and 0.77 for RFS were established by 200 cycles of bootstrap resampling for each of the two outcomes. CONCLUSION: Our data suggest that, in patients with EGEJC, pre- and post-treatment clinical parameters contribute to the establishment of prognostic nomograms of OS and RFS. Upon validation, these nomograms could prove useful in the clinic to individualize therapy.

Outcome of trimodality-eligible esophagogastric cancer patients who declined surgery after preoperative chemoradiation.

BACKGROUND: For patients with localized esophageal cancer (EC) who can withstand surgery, the preferred therapy is chemoradiation followed by surgery (trimodality). However, after achieving a clinical complete response [clinCR; defined as both post-chemoradiation endoscopic biopsy showing no cancer and physiologic uptake by positron emission tomography (PET)], some patients decline surgery. The literature on the outcome of such patients is sparse. METHOD: Between 2002 and 2011, we identified 622 trimodality-eligible EC patients in our prospectively maintained databases. All patients had to be trimodality eligible and must have completed preoperative staging after chemoradiation that included repeat endoscopic biopsy and PET among other routine tests. RESULTS: Out of 622 trimodality-eligible patients identified, 61 patients (9.8%) declined surgery. All 61 patients had a clinCR. The median age was 69 years (range 47-85). Males (85.2%) and Caucasians (88.5%) were dominant. Baseline stage was II (44.2%) or III (52.5%), and histology was adenocarcinoma (65.6%) or squamous cell carcinoma (29.5%). Forty-two patients are alive at a median follow-up of 50.9 months (95% CI 39.5-62.3). The 5-year overall and relapse-free survival rates were 58.1 ± 8.4 and 35.3 ± 7.6%, respectively. Of 13 patients with local recurrence during surveillance, 12 had successful salvage resection. CONCLUSION: Although the outcome of 61 EC patients with clinCR who declined surgery appears reasonable, in the absence of a validated prediction/prognosis model, surgery must be encouraged for all trimodality-eligible patients.

Clinical Significance of [18F] Fluoro-2-Deoxy-d-Glucose/Computed Tomographic Avid Hilar Lymph Nodes in Esophageal Carcinoma Patients.

BACKGROUND: The assumption that increased [18F] fluoro-2-deoxy-d-glucose (FDG) uptake in hilar nodes on positron emission tomography/computed tomography (PET/CT) imaging is indicative of distant metastasis can result in palliative rather than curative care in patients with esophageal cancer. This study aimed to determine the significance of increased FDG uptake in hilar nodes in patients with potentially curable, locally advanced disease at initial staging. METHODS: We included patients with biopsy specimen-proven esophageal carcinoma who had pretreatment FDG-PET/CT at initial staging and follow-up imaging >1 year. We excluded patients with distant hematogeneous metastases. Hilar nodes were considered concerning for metastatic disease when the maximum standardized uptake value was >2.5 or FDG uptake was visually greater than the mediastinal background. RESULTS: We reviewed FDG-PET CT scans from 806 patients treated for esophageal cancer from 2010 to 2018 and identified 42 patients with FDG-avid hilar adenopathy. Thirteen patients underwent histologic assessment, and 29 were monitored with imaging. None of the 42 patients had distant metastatic disease on the initial workup, and all were treated curatively. In follow-up, 2 of 42 patients eventually manifested hilar nodal metastases after treatment; 1 who had a biopsy specimen-negative hilar node at initial staging and another who did not have a biopsy of the hilar node. CONCLUSIONS: Increased FDG uptake in hilar nodes in patients with localized esophageal cancer was not indicative of nonregional nodal metastasis. Patients in these situations should be approached with curative intent. The need for biopsy of FDG-avid hilar nodes in this cohort should be carefully considered due to the low diagnostic utility.

Pitfalls and Pearls in Esophageal Carcinoma.

The management of patients with esophageal carcinoma (EC) requires accurate clinical staging and post-therapeutic evaluation. Currently, esophagogastroduodenoscopy/endoscopic ultrasound (EGD/EUS), endoscopic ultrasound-fine needle aspiration (EUS-FNA), computed tomography (CT), 18F- fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance (MR) imaging are used for the initial clinical staging, evaluation of therapeutic response and follow-up in patients with EC. However, there are limitations and pitfalls that are commonly encountered when imaging these patients that can limit accurate assessment. Knowledge of the limitations and pitfalls associated with the use of these different imaging modalities is essential in avoiding misinterpretation and guaranteeing the appropriate management for patient with EC.

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial.

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage III NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The NRG-LU001 randomized clinical trial was an open-label, phase 2 study conducted from August 24, 2014, to December 15, 2016. Patients without diabetes who were diagnosed with unresectable stage III NSCLC were stratified by performance status, histology, and stage. The setting was international and multi-institutional. This study examined prespecified endpoints, and data were analyzed on an intent-to-treat basis. Data were analyzed from February 25, 2019, to March 6, 2020. INTERVENTIONS: Chemoradiation and consolidation chemotherapy with or without metformin. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year progression-free survival (PFS), designed to detect 15% improvement in 1-year PFS from 50% to 65% (hazard ratio [HR], 0.622). Secondary end points included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity per Common Terminology Criteria for Adverse Events, version 4.03. RESULTS: A total of 170 patients were enrolled, with 167 eligible patients analyzed after exclusions (median age, 64 years [interquartile range, 58-72 years]; 97 men [58.1%]; 137 White patients [82.0%]), with 81 in the control group and 86 in the metformin group. Median follow-up was 27.7 months (range, 0.03-47.21 months) among living patients. One-year PFS rates were 60.4% (95% CI, 48.5%-70.4%) in the control group and 51.3% (95% CI, 39.8%-61.7%) in the metformin group (HR, 1.15; 95% CI, 0.77-1.73; P = .24). Clinical stage was the only factor significantly associated with PFS on multivariable analysis (HR, 1.79; 95% CI, 1.19-2.69; P = .005). One-year overall survival was 80.2% (95% CI, 69.3%-87.6%) in the control group and 80.8% (95% CI, 70.2%-87.9%) in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at 1 or 2 years. No significant difference in adverse events was observed between treatment groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to concurrent chemoradiation was well tolerated but did not improve survival among patients with unresectable stage III NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02186847.