Immune biomarkers and response to checkpoint inhibition of BRAFV600 and BRAF non-V600 altered lung cancers.

BACKGROUND: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours. METHODS: Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020. RESULTS: In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS). CONCLUSIONS: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.

Lung cancer screening in patients with previous malignancy: Is this cohort at increased risk for malignancy?

OBJECTIVES: To determine the rate of second primary lung cancer (SPLC) and describe the clinical characteristics and radiological findings in individuals with a prior history of cancer presenting to a low-dose computed tomography (LDCT) lung cancer screening program at a tertiary cancer center. METHODS: Patients with a previous history of malignancy, a life expectancy ≥ 5 years referred for CT lung cancer screening between May 2, 2011, and November 28, 2018, were included. Demographics regarding risk factors including smoking history and prior history of thoracic radiation were collected. CT scan features assessed nodule size, morphologic features, and number. The Lung-CT Reporting and Data System (Lung-RADS) scoring system was retrospectively applied to studies performed before October 2014 and prospectively applied to remainder of studies. Data was collected in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner. RESULTS: A total of 543 patients were studied (mean age of 66 years). All had a previous history of cancer, most commonly breast cancer 205 (38%), head and neck cancer 105 (19%), and lung cancer 87 (16%). Of screening CTs performed, 17.5% were positive screening study results as per Lung-RADS scoring system. SPLC was diagnosed in 35 patients (6.4%) with 21 prevalence cancers detected and 14 interval cancers detected in subsequent screening rounds. CONCLUSIONS: The rate of screen-detected SPLC in patients with prior malignancy is higher than reported rates seen in historical prospective screening studies. Our study suggests the need for prospective research to evaluate any mortality benefit that screening may have in this population. KEY POINTS: • The rate of screen-detected second primary lung cancer in patients with prior malignancy is higher than reported rates seen in historical prospective randomized lung cancer screening studies in a general screened population. • Patients with a prior malignancy undergoing lung cancer screening have higher rates of positive screening studies and higher rates of invasive diagnostic procedures than those reported in a general screening population. • Prospective research is required to evaluate if screening offers a mortality benefit in this population.

Perfusion defects on dual-energy CTA in patients with suspected pulmonary embolism correlate with right heart strain and lower survival.

OBJECTIVES: To evaluate the utility of perfusion defects on dual-energy CT angiograms (DECTA) in assessing the clinical severity of pulmonary embolism (PE). METHODS: We retrospectively reviewed 1136 consecutive diagnostic DECTA exams performed on patients with suspected PE between January 2014 and September 2014. Presence and location of obstructive and non-obstructive PE, right ventricular to left ventricular ratio (RV/LV ratio), and inferior vena cava (IVC) backflow were recorded. Iodine maps were reviewed to establish the presence of perfusion defect and its extent was determined through a score-based segmental impaired perfusion. Subsequently, the perfusion defect scores were correlated with clinical parameters including vital signs, electrocardiogram (ECG) abnormalities, echocardiogram findings, troponin, and brain natriuretic peptide (bnp) levels. Clinical information regarding primary cancer diagnosis, oncologic stage, and date of death if applicable was also recorded. RESULTS: Of the 1136 diagnostic iodine maps, 96 of these patients had perfusion defects on iodine maps. After uni- and multivariate analysis, significant correlation was found between the presence of a perfusion defect and RV/LV ratio (p = 0.05), IVC backflow (p = 0.03), elevated troponin (p = 0.03), and right heart dysfunction as determined on an echocardiogram (p = 0.05). The greater the perfusion defect score, the higher the likelihood of IVC backflow (p = 0.005) and obstructive PE (p = 0.002). When adjusted for oncologic stage, patients with a perfusion defect and a higher perfusion defect score had a higher mortality rate (p = 0.005). CONCLUSION: The presence of a perfusion defect correlates with several parameters evaluating PE severity. A perfusion defect and higher perfusion defect score were associated with a lower survival. KEY POINTS: • Detection of perfusion defects on dual-energy CT angiograms and its extent correlates with right heart strain in the setting of pulmonary embolism. • The presence and extent of a perfusion defect in patients with pulmonary embolism are associated with lower survival.

Management of Pulmonary Nodules in Oncologic Patients: AJR Expert Panel Narrative Review.

Cancer survivors are at higher risk than the general population for development of a new primary malignancy, most commonly lung cancer. Current lung cancer screening guidelines recommend low-dose chest CT for high-risk individuals, including patients with a history of cancer and a qualifying smoking history. However, major lung cancer screening trials have inconsistently included cancer survivors, and few studies have assessed management of lung nodules in this population. This narrative review highlights relevant literature and provides expert opinion for management of pulmonary nodules detected incidentally or by screening in oncologic patients. In patients with previously treated lung cancer, a new nodule most likely represents distant metastasis from the initial lung cancer or a second primary lung cancer; CT features such as nodule size and composition should guide decisions regarding biopsy, PET/CT, and CT surveillance. In patients with extrapulmonary cancers, nodule management requires individualized risk assessment; smoking is associated with increased odds of primary lung cancer, whereas specific primary cancer types are associated with increased odds of pulmonary metastasis. Nonneoplastic causes, such as infection, medication toxicity, and postradiation or postsurgical change, should also be considered. Future prospective studies are warranted to provide evidence-based data to assist clinical decision-making in this context.

Computed tomography features of local pleural recurrence in patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy.

OBJECTIVE: This study was conducted in order to describe the computed tomography (CT) features of local pleural recurrence in patients with malignant pleural mesothelioma undergoing intensity-modulated pleural radiation therapy (IMPRINT) as part of multimodality treatment. METHODS: In this observational study, 58 patients treated with IMPRINT between September 21, 2004, and December 1, 2014 were included. Baseline and follow-up CT scans were qualitatively assessed. On follow-up scans, pleural thickening was categorized as unchanged, decreased, or new/increased. New/increased pleural abnormality was subcategorized as diffuse smooth pleural thickening, diffuse nodular pleural thickening, focal pleural nodule, or multiple pleural nodules. To identify features more frequently present at the time of local recurrence, follow-up scans with local recurrence were matched to four control scans; exact conditional logistic regression was performed. RESULTS: Twenty-one (36%) patients had local pleural recurrence and 20 (34%) patients had nonpleural recurrence; 3 patients had both types of recurrence. The 1-year cumulative incidence rate of local recurrence was 27% (95% confidence interval 15, 39). On follow-up scans, three patterns of pleural abnormality were significantly associated with local recurrence: new/increased multiple pleural nodules (10 (48%) positive scans vs 0 control scans), new/increased diffuse nodular pleural thickening (7 (33%) positive scans vs 1 (1%) control scans), and new/increased focal pleural nodule (3 (14%) positive scans vs 1 (1%) control scan) (p < 0.001 for all). CONCLUSIONS: Multiple new/increased pleural nodules are the feature most commonly present at local recurrence following IMPRINT; however, any pattern of increased nodular pleural thickening is suspicious. KEY POINTS: • In patients with mesothelioma receiving intensity-modulated pleural radiation as part of multimodality therapy, increasing multiple pleural nodules is the computed tomography feature most commonly present at local recurrence. • In these patients, any CT pattern of increased nodular pleural thickening should be considered suspicious for local recurrence. • The most common sites of nonpleural recurrence were lung parenchyma, thoracic lymph nodes, and peritoneum.

CT Characteristics of Non-Small Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangement: A Systematic Review and Meta-Analysis.

OBJECTIVE. The purpose of this study was to perform a systematic review and meta-analysis regarding CT features of non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. MATERIALS AND METHODS. The PubMed and Embase databases were searched up to February 20, 2019. Studies that evaluated CT features of NSCLC with and without ALK rearrangement was included. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The association between CT features and ALK rearrangement was pooled in the form of the odds ratio (OR) or the mean difference (MD) using the random-effects model. Heterogeneity was examined using the inconsistency index (I2). Publication bias was examined using funnel plots and Egger tests. RESULTS. Sixteen studies were included, consisting of 3113 patients with NSCLC. The overall prevalence of patients with ALK rearrangement was 17% (528/3113). Compared with NSCLC without ALK rearrangement, on CT images those with ALK rearrangement were more frequently solid (OR = 2.86), central in location (OR = 2.72), and 3 cm or smaller (OR = 0.57); had lower contrast-enhanced CT attenuation (MD = -4.79 HU); more frequently had N2 or N3 disease (OR = 5.63), lymphangitic carcinomatosis (OR = 3.46), pleural effusion (OR = 1.91), or pleural metastasis (OR = 1.81); and less frequently had lung metastasis (OR = 0.66). Heterogeneity varied among CT features (I2 = 0-80%). No significant publication bias was seen (p = 0.15). CONCLUSION. NSCLC with ALK rearrangement had several distinctive CT features compared with that without ALK rearrangement. These CT biomarkers may help identify patients likely to have ALK rearrangement.

Dual-Energy CT Angiography for Detection of Pulmonary Emboli: Incremental Benefit of Iodine Maps.

Purpose To determine if there is added benefit of using iodine maps from dual-energy (DE) CT in addition to conventional CT angiography images to diagnose pulmonary embolism (PE). Materials and Methods In this retrospective analysis, 1144 consecutive dual-energy CT angiography examinations performed from January through September 2014 at an oncologic referral center to evaluate for PE were reviewed. The 1144 examinations included 1035 patients (mean age, 58.7 years; range, 15-99 years). First, the location, level, and type (occlusive vs nonocclusive) of PEs on conventional CT angiograms were recorded. Iodine maps were then reviewed for defects suggestive of PE. Last, CT angiograms were rereviewed to detect additional PEs suggested by the iodine map. Consensus reviews were performed for examinations with PEs. The confidence interval of percentages was calculated by using the Clopper-Pearson method. Results On 147 of 1144 (12.8%) CT angiograms, a total of 372 PEs were detected at initial review. After review of the DE CT iodine map, 27 additional PEs were found on 26 of 1144 CT angiograms (2.3%; 95% confidence interval [CI]: 1.5%, 3.3%). Of the 27 additional PEs, six (22.2%) were segmental, 21 (77.8%) were subsegmental, 24 (88.9%) were occlusive, and three (11.1%) were nonocclusive. Eleven of 1144 (1.0%; 95% CI: 0.5%, 1.7%) CT angiograms had a new diagnosis of PE after review of the DE CT iodine maps. Conclusion Dual-energy CT iodine maps show a small incremental benefit for the detection of occlusive segmental and subsegmental pulmonary emboli. © RSNA, 2018.

Prognostic utility of differential tissue characterization of cardiac neoplasm and thrombus via late gadolinium enhancement cardiovascular magnetic resonance among patients with advanced systemic cancer.

BACKGROUND: Late gadolinium enhancement (LGE-) cardiovascular magnetic resonance (CMR) is well-validated for cardiac mass (CMASS) tissue characterization to differentiate neoplasm (CNEO) from thrombus (CTHR): Prognostic implications of CMASS subtypes among systemic cancer patients are unknown. METHODS: CMASS + patients and controls (CMASS -) matched for cancer diagnosis and stage underwent a standardized CMR protocol, including LGE-CMR (IR-GRE) for tissue characterization and balanced steady state free precession cine-CMR (SSFP) for cardiac structure/function. CMASS subtypes (CNEO, CTHR) were respectively defined by presence or absence of enhancement on LGE-CMR; lesions were quantified for tissue properties (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR) and size. Clinical follow-up was performed to evaluate prognosis in relation to CMASS etiology. RESULTS: The study population comprised 126 patients with systemic neoplasms referred for CMR, of whom 50% (n = 63) had CMASS + (CNEO = 32%, CTHR = 18%). Cancer etiology differed between CNEO (sarcoma = 20%, lung = 18%) and CTHR (lymphoma = 30%, GI = 26%); cardiac function (left ventricular ejection fraction: 63 ± 9 vs. 62 ± 10%; p = 0.51∣ right ventricular ejection fraction: 53 ± 9 vs. 54 ± 8%; p = 0.47) and geometric indices were similar (all p = NS). LGE-CMR tissue properties assessed by CNR (13.1 ± 13.0 vs. 1.6 ± 1.0; p < 0.001) and SNR (29.7 ± 20.4 vs. 15.0 ± 11.4, p = 0.003) were higher for CNEO, consistent with visually-assigned diagnostic categories. CTHR were more likely to localize to the right atrium (78% vs. 25%, p < 0.001); nearly all (17/18) were associated with central catheters. Lesion size (17.3 ± 23.8 vs. 2.0 ± 1.5 cm2; p < 0.001) was greater with CNEO vs. CTHR, as was systemic disease burden (cancer-involved organs: 3.6 ± 2.0 vs. 2.3 ± 2.1; p = 0.02). Mortality during a median follow-up of 2.5 years was markedly higher among patients with CNEO compared to those with CTHR (HR = 3.13 [CI 1.54-6.39], p = 0.002); prognosis was similar when patients were stratified by lesion size assessed via area (HR = 0.99 per cm2 [CI 0.98-1.01], p = 0.40) or maximal diameter (HR = 0.98 per cm [CI 0.91-1.06], p = 0.61). CTHR conferred similar mortality risk compared to cancer-matched controls without cardiac involvement (p = 0.64) whereas mortality associated with CNEO was slightly higher albeit non-significant (p = 0.12). CONCLUSIONS: Among a broad cancer cohort with cardiac masses, CNEO defined by LGE-CMR tissue characterization conferred markedly poorer prognosis than CTHR, whereas anatomic assessment via cine-CMR did not stratify mortality risk. Both CNEO and CTHR are associated with similar prognosis compared to CMASS - controls matched for cancer type and disease extent.

Intracardiac Embolized Prostate Brachytherapy Seeds: Imaging Features in Patients Undergoing Electrocardiogram-Gated Cardiac Computed Tomography.

OBJECTIVE: This study aims to provide the first description of the computed tomographic (CT) appearances of intracardiac embolized brachytherapy seeds in patients undergoing electrocardiogram (ECG)-gated cardiac CT. METHODS: The institutional Picture Archive and Communication System was searched for male patients who underwent enhanced ECG-gated cardiac CT, and reports were searched for the key words "metallic," "prostate," "brachytherapy," "radiation," "embolized," and "radioactive." Each study was identified and examined for an intracardiac metallic object conforming to the size of a prostate seed. RESULTS: Between January 01, 2005, and June 30, 2014, a total of 3206 male patients underwent ECG-gated cardiac CT. Five patients (0.15%) had a history of prostate cancer and an intracardiac metallic object with CT imaging characteristics consistent with an embolized prostate seed. In all 5 patients, the seeds were embedded in the trabeculations of the inferior aspect of the basal right ventricular free wall. CONCLUSIONS: Intracardiac embolized brachytherapy seeds appear as small objects with surrounding metallic artifact characteristically embedded in the inferior aspect of the basal right ventricular free wall.

18F-FDG-PET/CT is of limited value in primary staging of early stage cervical cancer.

PURPOSE: To assess the clinical benefit of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) in evaluating pelvic lymph nodes in patients with early stage cervical cancer (FIGO stage 1a­1b1), who have magnetic resonance imaging (MRI)-defined lymph node negative disease, with histopathologic results as the reference standard. MATERIALS AND METHODS: We assessed one hundred and seventy nine sequential 18F-FDG-PET/CT scans in women with newly diagnosed cervical carcinoma between January 2009 and September 2011. 47 of these patients had early stage disease (FIGO stage 1a­1b1) with no suspicious lymph nodes on MRI. 18F-FDG-PET/CT images were analyzed and histopathological findings (pelvic lymph node resection) served as the reference standard. RESULTS: The median age of patients was 48 (range 22­86) years. 66 % had squamous histotype. Median number of nodes dissected per patient was 21 (range 8­47), 2 of 47 patients had nodal metastases (4.25 %). All patients in this group had no suspicious lymph nodes on 18F-FDG-PET/CT. Overall patient based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG-PET/CT for detection of nodal disease were 0 %, 100 %, 0 %, 96 %, and 96 % respectively. CONCLUSION: Pathologic validation of 18F-FDG-PET/CT imaging demonstrates little value for 18F-FDG-PET/CT in patients with early stage (FIGO stage 1a­1b1) MRI-defined lymph node negative cervical carcinoma. Since the likelihood of metastatic nodal disease is very low in women with stage 1a­1b1 cervical cancer, we believe that 18F-FDG-PET/CT should not have a role in the routine pre-treatment evaluation of these women.

Does obesity preclude lumbar puncture with a standard spinal needle? The use of computed tomography to measure the skin to lumbar subarachnoid space distance in the general hospital population.

OBJECTIVES: Failed lumbar puncture (LP) is a common indication for referral for radiologically guided LP. This study aims to evaluate what percentage of the hospital population would fail an LP using a standard 9-cm needle because of obesity and a skin to subarachnoid space distance greater than 9 cm. METHODS: Images of 402 consecutive patients undergoing computed tomography of the abdomen and pelvis were reviewed. Skin to subarachnoid space distance was calculated using sagittal images. A survey was conducted among junior hospital doctors to assess their experience of performing lumbar puncture in obese patients. RESULTS: Four hundred patients were included. Fifty-five patients (13.8 %) had a skin to subarachnoid space distance greater than 9 cm. Intra-abdominal fat, subcutaneous fat and abdominal girth correlated with distance between the skin and subarachnoid space. Among junior doctors, 68.3 % (n = 41) reported LP failure on an obese patient; 78.4 % (n = 47) were unaware of the existence of a longer needle and 13.3 % (n = 8) had experience using a longer needle. CONCLUSIONS: A significant proportion of the hospital population will fail LP with a standard length spinal needle. Selecting a longer needle may be sufficient to successfully complete LP in obese patients. KEY POINTS: • Lumbar puncture failure commonly leads to referral for an image-guided procedure • Standard lumbar puncture may fail in 13.8 % of patients due to obesity • 78.4 % of trainee doctors are unaware of the existence of longer spinal-needles • Using longer spinal needles may allow successful LP in obese patients.

Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy.

Background: Androgen deprivation therapy (ADT) is a common treatment modality for men with prostate cancer. Increases in adipose tissue mass and decreases in skeletal muscle mass are known on-target adverse effects of standard ADT. The effects of newer agents such as abiraterone acetate (ABI) and enzalutamide (ENZA) on body composition and how these compare with standard luteinizing hormone-releasing hormone agonists (aLHRHs) are unclear. Objective: To assess the effects of different forms of androgen deprivation therapy on body composition in men with prostate cancer. Design setting and participants: Using a retrospective design, 229 patients receiving aLHRHs alone (n = 120) or in combination with ABI (n = 53) or ENZA (n = 56) were studied. Outcome measurements and statistical analysis: Muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at baseline, 6 mo, and 18 mo after initiating therapy using a cross-sectional densitometry analysis performed on standard of care computed tomography images. Response trajectories for all treatment groups were calculated via a two-way analysis of variance post hoc test, for both within-group and between-group differences. Results and limitations: Treatment with aLHRHs, ABI, and ENZA was associated with a median muscle volume loss of -1.4%, -4.8%, and -5.5% at 6 mo, and -7.1%, -8.1%, and -8.3% at 18 mo, respectively. Therapy with aLHRHs was associated with minimal changes in VAT (0.3% at 6 mo and -0.1% at 18 mo). ABI therapy was associated with significant increases in VAT at 6 mo (4.9%) but not at 18 mo (0.5%), and ENZA therapy was associated with significant decreases in VAT (-4.6% at 6 mo and -5.4% at 18 mo). With respect to SAT, treatment with aLHRHs was associated with increases over time (8.6% at 6 mo and 4.7% at 18 mo), ABI was associated with decreases over time (-3.6% at 6 mo and -6.8% at 18 mo), and ENZA had no clear effects (1.7% at 6 mo and 3.3% at 18 mo). Conclusions: ADT regimens cause significant short-term losses in muscle mass, with the most rapid effects occurring with ABI and ENZA. The three regimens have disparate effects on SAT and VAT, suggesting distinct roles of androgens in these tissues. Patient summary: Androgen deprivation therapy alters body composition in men with prostate cancer. Abiraterone and enzalutamide are associated with losses in muscle mass compared with luteinizing hormone-releasing hormone agonists. These treatments impact subcutaneous and visceral fat mass, suggesting distinct roles of androgens in these tissues.

Life-threatening rupture of a renal angiomyolipoma in a patient taking over-the-counter horse chestnut seed extract.

BACKGROUND: Alternative medical therapies are increasingly being prescribed due to their good safety profile and perceived limited side effects. They are often unregulated and prescribed over the counter. One such medication is horse chestnut seed extract (HCSE), which is used for the treatment of chronic venous insufficiency and is known to affect blood coagulation. Angiomyolipoma (AML) is a benign fat-containing mesenchymal tumor of the kidney. It is often found incidentally and in most cases can be managed conservatively. Rupture of the kidney with hemorrhage is a well-known complication that may be serious and life-threatening. Known risk factors for hemorrhage include anticoagulation as well as pregnancy, increased size of the lesion, high lesion vascularity, and aneurysm formation within the tumor. OBJECTIVES: The aim is to raise awareness of potential HCSE-induced anticoagulation, including, as in the case presented, acute renal AML hemorrhage. CASE REPORT: The case of a patient taking HCSE for venous insufficiency is presented. The patient suffered a life-threatening rupture of the kidney in the presence of known renal AML. She underwent emergency embolization with a successful outcome. Because HCSE-containing products are thought to be generally safe in the treatment of chronic venous insufficiency, it is important to be mindful of their potential anticoagulant properties and, therefore, their relative contraindication both in patients taking other anticoagulants and those with known renal AML. CONCLUSION: We demonstrate a potentially life-threatening association between HSCE-containing products and renal AML, highlighting the risk associated with HSCE-induced anticoagulation.

Brain radiotherapy, tremelimumab-mediated CTLA-4-directed blockade +/- trastuzumab in patients with breast cancer brain metastases.

Breast cancer brain metastases (BCBM) are a common and devastating complication of metastatic breast cancer with conventional systemic therapies demonstrating limited effectiveness. Consequently, radiotherapy (RT) ± surgery remains the cornerstone of BCBM management. Because preclinical and clinical evidence indicate that immune checkpoint blockade (ICB) may synergize with RT to promote systemic tumor regression, we explored the safety and efficacy of RT and concurrent tremelimumab-mediated cytotoxic T-lymphocyte associated protein 4 (CTLA-4) ICB with tremelimumab ± HER2-directed therapy with trastuzumab for BCBM. Eligible patients had BCBM indicated for brain RT. A Simon two-stage design was adopted to evaluate the efficacy of tremelimumab and RT in 20 patients with human epidermal growth factor receptor normal (HER2-) BCBM. The safety of concurrent RT, tremelimumab, and trastuzumab was evaluated in a cohort of 6 HER2+ patients. The primary endpoint was 12-week non-central nervous system (CNS) disease control rate (DCR). Secondary endpoints included safety, survival, and CNS response. Exploratory correlatives included characterization of peripheral blood immune responses among exceptional responders. Tremelimumab plus RT ± trastuzumab was tolerated with no treatment-related grade 4 adverse events reported. The 12-week non-CNS DCR was 10% (2/20) in the HER2- cohort and 33% (2/6) in the HER2+ cohort. One patient with HER2+ disease experienced a durable partial response with evidence of peripheral T-cell activation. Thus, tremelimumab and RT ± trastuzumab was tolerated. Although modest clinical activity was observed in the HER2- efficacy cohort, encouraging responses were observed in the HER2+ safety cohort. Consequently, a trial to determine efficacy in HER2+ BCBM is planned.Clinical Trial Registration Number: NCT02563925.

Percutaneous computed tomography guided biopsy of sub-solid pulmonary nodules: differentiating solid from ground glass components at the time of biopsy.

INTRODUCTION: This study assessed (i) the ability to identify the solid components of part-solid nodules (PSN) during computed tomography (CT) guided lung biopsy (CTGLB), (ii) the ability of CTGLB to assess the invasive nature of a nodule on pathology. MATERIALS AND METHODS: Sixty-nine nodules were studied in 68 patients who underwent CTGLB between 1/1/2014 and 10/31/2015. Diagnostic CT images and CTGLB images were reviewed. On diagnostic CT images, nodules were classified as ground glass nodules (GGN) or PSNs. Nodule size, location, and percentage of solid component were recorded. At the time of biopsy, the ability to visualize the solid component of a PSN, depth of lesion from skin, and ability to identify the needle within the solid component were recorded. RESULTS: There were 42 (61%) part-solid nodules and 27 (39%) GGNs. During biopsy, it was possible to differentiate the solid from the ground glass components in 35 (83%) PSNs. Fifty-nine (86%) nodules were neoplastic based on biopsy pathology (all non-small cell lung carcinoma). Thirty-nine (66%) were resected. In all cases biopsy pathology and surgical pathology agreed regarding the presence of lung carcinoma. In 6 (15%) cases biopsy pathology demonstrated purely lepidic growth but had some non-lepidic growth on surgical pathology, including 2 cases with acinar growth as a dominant pattern. CONCLUSION: In most patients, the solid and ground glass components of a PSN were distinguishable when performing a CTGLB. In a minority of patients, discrepancy was noted between biopsy pathology and surgical pathology regarding the invasive nature of a nodule.

Intra- and inter-reader agreement of iRECIST and RECIST 1.1 criteria for the assessment of tumor response in patients receiving checkpoint inhibitor immunotherapy for lung cancer.

OBJECTIVES: To investigate the inter- and intra-reader agreement of immune Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) in patients with lung cancer treated with immunotherapy. MATERIALS AND METHODS: This retrospective study included 85 patients with lung cancer treated with PD-1 blockade. Four radiologists evaluated computed topography (CT) scans before and after initiation of immunotherapy using iRECIST and RECIST 1.1. Weighted kappa (k) with equal weights was used to assess the intra-reader agreement between 2 repeated reads on overall response at all time points, best overall response, and the response at the time point of progression, as well as the intra-reader agreement between iRECIST and RECIST. The inter-reader agreement was calculated using Light's kappa. RESULTS: Intra-reader agreement for overall response at all time points, best overall response, and time point of progression was substantial to almost perfect for both iRECIST and RECIST 1.1 (k = 0.651-0.983). Inter-reader agreement was substantial for iRECIST (κ = 0.657-0.742) while RECIST 1.1 was moderate to substantial (κ = 0.587-0.686). The level of inter-reader agreement was not higher on repeat read for iRECIST (κ = 0.677-0.709 and κ = 0.657-0.742 for first and second read, respectively) as well as for RECIST 1.1 (κ = 0.587-0.659 and κ = 0.633-0.686 for first and second read, respectively). Almost perfect agreement was observed between RECIST 1.1 and iRECIST at first (κ = 0.813-0.923) and second read (κ = 0.841-0.912). CONCLUSION: The inter- and intra-reader agreement of iRECIST is high and similar to RECIST 1.1 in patients with lung cancer treated with immunotherapy.

The effects of neoadjuvant chemotherapy and interval debulking surgery on body composition in patients with ovarian cancer.

BACKGROUND: The aim of this study was to quantify changes in body composition during ovarian cancer treatment and relate these changes to rates of complete gross resection (CGR). METHODS: One hundred two patients with stage III or IV ovarian cancer who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery were a part of a prospectively collected database that included computed tomography scans at three time points-diagnosis, following NACT, and following debulking surgery. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue volumes were obtained from a 30-mm volumetric slab beginning at the third lumbar vertebrae. RESULTS: Following NACT, skeletal muscle volume was significantly reduced (352.5 to 335.0 cm3, P < 0.001), whereas adiposity was unchanged. Body mass index (BMI) and skeletal muscle volume were significantly lower in patients who achieved CGR (P < 0.05). When these patients were stratified by BMI, the significant association of skeletal muscle to CGR was limited to patients with a BMI < 25 kg/m2 (P = 0.007). CONCLUSION: Skeletal muscle volume was significantly reduced in patients undergoing NACT for ovarian cancer. Non-overweight patients were more likely to achieve CGR if they had lower skeletal muscle volume. Use of volumetric-based measurement for ascertaining body composition should be explored further.