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1.
Clin Cancer Res ; 29(8): 1423-1428, 2023 04 14.
Article in English | MEDLINE | ID: mdl-36729110

ABSTRACT

PURPOSE: Primary and acquired resistance to osimertinib remain significant challenges for patients with EGFR-mutant lung cancers. Acquired EGFR alterations such as EGFR T790M or C797S mediate resistance to EGFR tyrosine kinase inhibitors (TKI) and combination therapy with dual EGFR TKIs may prevent or reverse on-target resistance. PATIENTS AND METHODS: We conducted two prospective, phase I/II trials assessing combination osimertinib and dacomitinib to address on-target resistance in the primary and acquired resistance settings. In the initial therapy study, patients received dacomitinib and osimertinib in combination as initial therapy. In the acquired resistance trial, dacomitinib with or without osimertinib was administered to patients with EGFR-mutant lung cancers with disease progression on osimertinib alone and evidence of an acquired EGFR second-site mutation. RESULTS: Cutaneous toxicities occurred in 93% (any grade) of patients and diarrhea in 72% (any grade) with the combination. As initial therapy, the overall response to the combination was 73% [95% confidence interval (CI), 50%-88%]. No acquired secondary alterations in EGFR were observed in any patients at progression. In the acquired resistance setting, the overall response was 14% (95% CI, 1%-58%). CONCLUSIONS: We observed no acquired secondary EGFR alterations with dual inhibition of EGFR as up-front treatment, but this regimen was associated with greater toxicity. The combination was not effective in reversing acquired resistance after development of a second-site acquired EGFR alteration. Our study highlights the need to develop better strategies to address on-target resistance in patients with EGFR-mutant lung cancers.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/genetics , Mutation , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Drug Resistance, Neoplasm/genetics , Aniline Compounds/pharmacology
2.
JTO Clin Res Rep ; 4(1): 100440, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36590015

ABSTRACT

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients with malignant pleural mesothelioma. Methods: This was a single-arm, investigator-initiated trial in patients who progressed on prior chemotherapy. Avelumab was delivered every other week, and SBRT was delivered to one lesion in three to five fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. The primary end point of the study was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 months of SBRT. Results: Thirteen assessable patients received a median of seven cycles (range: 2-26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and nausea/vomiting (n = 2). Conclusions: Combination avelumab plus SBRT seems tolerable on the basis of the prespecified toxicity end points of the first stage of this Simon two-stage design phase 1 study.

3.
Gynecol Oncol Rep ; 37: 100831, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34345644

ABSTRACT

OBJECTIVE: Since the approval of pembrolizumab for advanced or recurrent PD-L1 positive (CPS > 1%) cervical cancer, the clinical characteristics associated with response have remained undefined. We sought to characterize the clinicopathologic features of patients with advanced cervical cancer at our institution who derived durable clinical benefit from treatment with pembrolizumab. METHODS: We conducted a retrospective cohort study of 14 patients with recurrent or metastatic cervical cancer who received pembrolizumab monotherapy from August 2017 to November 2019 and were followed until November 1, 2020. Reviewed clinical data included age, histology, tumor molecular profiling results, stage at diagnosis, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 therapy, and outcomes. Treatment response was evaluated by computed tomography using RECIST v1.1 criteria. RESULTS: The objective response rate was 21% (n = 3), including two partial responses and one complete response. Two patients (14%) had stable disease of six months or greater, for an observed durable clinical benefit rate of 36%. When stratified by those who derived clinical benefit, metastatic spread to lung and/or lymph node only at baseline was associated with improved response to pembrolizumab (n = 7, p = 0.02) and associated with significantly improved PFS and OS. Tumor mutational burden was higher in those with durable clinical benefit compared to non-responders (median 12.7 vs. 3.5 mutations/megabase, p = 0.03). CONCLUSIONS: Our findings highlight clinical features that may select for a population most likely to benefit from pembrolizumab monotherapy and underscores the need for identification of additional biomarkers of response.

4.
Article in English | MEDLINE | ID: mdl-34250388

ABSTRACT

Inhibition of the MEK/ERK pathway is critical for Bcl-2-like protein 11 (BIM)-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-induced apoptosis, and dysregulation of this pathway may be a mechanism of acquired resistance. Therefore, MEK inhibition with trametinib and an EGFR TKI may resensitize tumors with acquired resistance. Limited targeted therapies are available after progression on EGFR TKIs, and it is in this setting that we completed a phase I/II study of erlotinib and trametinib. METHODS: Patients with metastatic EGFR-mutant lung adenocarcinoma and acquired resistance to an EGFR TKI received combination erlotinib 75 mg and trametinib 1.5 mg daily until progression or unacceptable side effects. The primary objective was objective response rate determined using RECIST version 1.1. RESULTS: Twenty-three patients were accrued; patients had received a median of two lines of prior TKI therapy (61% prior osimertinib), and 48% had acquired EGFR T790M. We confirmed one partial response (1/23, 4%, 95% CI, 0 to 22). The median progression-free survival was 1.8 months, and the median overall survival was 21 months. Diarrhea (87%), acneiform rash (87%), and fatigue (52%) were the most common treatment-related adverse events. Two patients who had tumor shrinkage both harbored a BRAF fusion. CONCLUSION: Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious. Future studies should focus on targeted therapies in molecularly selected populations. Acquired BRAF fusions in patients with EGFR-sensitizing mutations may be a molecular subset where EGFR and MEK combination therapy could be studied further.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Antineoplastic Agents/therapeutic use , ErbB Receptors/genetics , Erlotinib Hydrochloride/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Pyridones/therapeutic use , Pyrimidinones/therapeutic use , Adult , Aged , Aged, 80 and over , Drug Resistance, Neoplasm , Female , Humans , Male , Middle Aged
5.
Article in English | MEDLINE | ID: mdl-34250398

ABSTRACT

Patients with EGFR-mutant lung cancer have no approved targeted therapies after disease progression on first-line osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Preclinical studies suggest that tumors with both EGFR-sensitizing alteration and acquired second-site EGFR resistance alterations after treatment with osimertinib retain sensitivity to second-generation EGFR TKIs. We hypothesized that dacomitinib, a pan-human epidermal growth factor receptor TKI, may be effective in this setting. METHODS: In this phase II study, patients who had progressed on first-line osimertinib were treated with dacomitinib 45 mg orally daily until disease progression or intolerability. The primary end point was objective response rate. RESULTS: We enrolled 12 patients. Two partial responses were documented (17% objective response rate; 95% CI, 5 to 45). The median progression-free survival was 1.8 months (95% CI, 1.6 to not reached). One patient with an original sensitizing EGFR G719A mutation and one patient without molecular testing available had partial responses, whereas 0 of the 3 patients with second-site acquired EGFR resistance mutations (two C797S and one G724S) met the response criteria. The patient with EGFR G719A has an ongoing response at 17 months, which exceeds prior time on osimertinib (11 months). CONCLUSION: In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Quinazolinones/therapeutic use , Aged , Aged, 80 and over , Disease Progression , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Pilot Projects , Prospective Studies , Retreatment
6.
Eur Radiol ; 31(4): 2013-2021, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33048226

ABSTRACT

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.


Subject(s)
Pulmonary Embolism , Ventricular Dysfunction, Right , Angiography , Humans , Perfusion , Pulmonary Embolism/diagnostic imaging , Retrospective Studies , Ventricular Dysfunction, Right/diagnostic imaging
7.
JAMA Oncol ; 6(7): 1048-1054, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32463456

ABSTRACT

Importance: The combination of erlotinib and bevacizumab as initial treatment of epidermal growth factor receptor (EGFR [OMIM 131550])-mutant lung cancers improves progression-free survival (PFS) compared with erlotinib alone. Because osimertinib prolongs PFS compared with erlotinib, this trial was designed to study the combination of osimertinib and bevacizumab as first-line treatment. Objectives: To determine the safety and tolerability of osimertinib and bevacizumab combination treatment and assess the 12-month PFS of the combination in patients with metastatic EGFR-mutant lung cancers. Design, Setting, and Particiants: From August 15, 2016, to May 15, 2018, 49 patients with metastatic EGFR-mutant lung cancers were enrolled in this interventional clinical trial, conducted at a single academic cancer center. In the phase 1 portion of the study, a standard 3 + 3 dose de-escalation design was used to determine the maximum tolerated dose of osimertinib and bevacizumab. In the phase 2 portion of the study, patients were treated at the maximum tolerated dose defined in the phase 1 portion. Statistical analysis was performed from August 1 to October 1, 2019. Interventions: All patients received osimertinib, 80 mg daily, and bevacizumab, 15 mg/kg once every 3 weeks. Main Outcomes and Measures: The primary objective of the phase 2 portion of the study was to determine the number of patients receiving the combination of osimertinib and bevacizumab who were progression free at 12 months. Secondary end points included overall response rate, median PFS, overall survival, and definition of the toxic effects of the combination treatment. Results: Among the 49 patients in the study (34 women; median age, 60 years [range, 36-83 years]), PFS at 12 months was 76% (95% CI, 65%-90%). The overall response rate was 80% (95% CI, 67%-91%), and median PFS was 19 months (95% CI, 15-24 months). Of the 6 patients with measurable central nervous system disease, all had a partial or complete central nervous system response. Persistent detection of EGFR-mutant circulating tumor (ct)DNA at 6 weeks was associated with shorter median PFS (clearance at 6 weeks, 16.2 months [95% CI, 13 months to not reached]; and no clearance at 6 weeks, 9.8 months [95% CI, 4 months to not reached]; P = .04) and median overall survival (clearance at 6 weeks, not reached; and no clearance at 6 weeks, 10.1 months [95% CI, 6 months to not reached]; P = .002). Identified mechanisms of resistance included squamous cell transformation (n = 2) pleomorphic transformation (n = 1), and acquired EGFR L718Q (n = 1) and C797S (n = 1) mutations. Conclusions and Relevance: The combination of osimertinib and bevacizumab met the study's prespecified effectiveness end point. Persistent EGFR-mutant circulating tumor DNA at 6 weeks was associated with early progression and shorter survival. A randomized phase 3 study comparing osimertinib and bevacizumab with osimertinib alone is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT02803203.


Subject(s)
Acrylamides/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Aniline Compounds/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Circulating Tumor DNA/blood , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Mutation , Progression-Free Survival
8.
J Clin Oncol ; 38(15): 1655-1663, 2020 05 20.
Article in English | MEDLINE | ID: mdl-32053428

ABSTRACT

PURPOSE: To analyze long-term outcomes after treatment discontinuation of anti-programmed death-1 (anti-PD-1) therapy in a cohort of patients with melanoma with the longest follow-up yet available to our knowledge, including a majority of patients treated outside of a clinical trial. We also assessed efficacy of retreatment with anti-PD-1 therapy with or without ipilimumab in relapsing patients. METHODS: We retrospectively analyzed all patients with nonuveal, unresectable stage III/IV melanoma treated with single-agent anti-PD-1 therapy at Memorial Sloan Kettering from 2009-2018 who had discontinued treatment and had at least 3 months of follow-up after discontinuation (n = 396). Overall survival for patients with complete response (CR) was calculated from time of CR. Time to treatment failure for patients with CR was time from CR to the next melanoma treatment or death. RESULTS: CRs were seen in 102 of 396 patients (25.8%). The median number of months of treatment after CR was zero (range, stopped before CR to 26 months after CR). With a median follow-up of 21.1 months from time of CR in patients who did not relapse, the probability of being alive and not needing additional melanoma therapy at 3 years was 72.1%. There was no significant association between treatment duration and relapse risk. In multivariable analysis, CR was associated with M1b disease and cutaneous versus mucosal or acral primaries. Among the 78 patients (of 396) retreated after disease progression, response was seen in 5 of 34 retreated patients with single-agent anti-PD-1 therapy and 11 of 44 patients escalated to anti-PD-1 plus ipilimumab. CONCLUSION: In our cohort, most patients discontinued treatment at the time of CR. Most CRs were durable but the probability of treatment failure was 27% at 3 years. Responses to retreatment were infrequent. The optimal duration of treatment after CR is not yet established.


Subject(s)
Melanoma/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Retreatment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Melanoma/pathology , Middle Aged , Retrospective Studies , Young Adult
9.
Int J Gynecol Cancer ; 29(9): 1377-1380, 2019 11.
Article in English | MEDLINE | ID: mdl-31575614

ABSTRACT

OBJECTIVES: To assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis. METHODS: We evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis. RESULTS: Of 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2-72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3-7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1-1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4-95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively. CONCLUSIONS: In our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.


Subject(s)
Cystadenocarcinoma, Serous/pathology , Lymphadenopathy/pathology , Ovarian Neoplasms/pathology , Adult , Aged , Chemotherapy, Adjuvant , Cohort Studies , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/surgery , Female , Humans , Lymph Nodes/pathology , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Prognosis , Progression-Free Survival , Retrospective Studies , Survival Rate
10.
Br J Radiol ; 92(1104): 20190473, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31386554

ABSTRACT

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis which can have a broad range of clinical and radiological presentations. Typically, ECD affects multiple organ systems, with skeletal involvement present in almost all ECD patients and cardiothoracic manifestations in more than half. Cardiac and thoracic involvement contributes significantly to morbidity and mortality in affected patients and may have prognostic implications. The diagnosis of ECD can be challenging due to its rarity and similarity to other systemic disease processes. Although the diagnosis can be suggested on imaging, histopathology and immunohistochemistry are required for confirmation. We describe the multimodal imaging features of mediastinal, cardiac, pleural and lung parenchymal ECD. This review identifies the most common radiological manifestations of cardiac and thoracic ECD on contrast-enhanced CT, fluorine18-fludeoxyglucose positron emission tomography/CT and cardiac MRI, and highlights the role of these cross-sectional techniques in disease diagnosis.


Subject(s)
Erdheim-Chester Disease/diagnostic imaging , Heart Diseases/diagnostic imaging , Lung Diseases/diagnostic imaging , Mediastinal Diseases/diagnostic imaging , Multimodal Imaging/methods , Contrast Media , Erdheim-Chester Disease/complications , Fluorodeoxyglucose F18 , Heart Diseases/etiology , Humans , Lung Diseases/etiology , Magnetic Resonance Imaging , Mediastinal Diseases/etiology , Pleural Diseases/diagnostic imaging , Pleural Diseases/etiology , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals , Tomography, X-Ray Computed/methods
11.
Clin Imaging ; 57: 110-114, 2019.
Article in English | MEDLINE | ID: mdl-31207563

ABSTRACT

PURPOSE: To evaluate for stability of perifissural nodules (PFNs) in a dedicated oncologic population. METHODS: A retrospective review of 500 computed tomography (CT) chests from oncologic patients at our tertiary care cancer center with at least a three year follow up yielded 76 patients with PFNs. Patients with metastases on baseline CT chest were excluded (n = 14) as the presence of a PFN would not be clinically relevant, thus our final patient cohort was 62 patients with a total of 112 PFNs. PFN features, clinical features, and ancillary information was recorded from the CT and the electronic medical record for all patients. The two patient cohorts-stable or decreased PFN vs. increased PFN-were then compared. RESULTS: 112 PFNs were examined in 62 patients with a median follow up interval of 5.7 years. Of 62 patients, 59 (95.2%, 95% CI: 86.5, 99.0) had decreased/stable PFNs on follow up scan (median follow up 5.6 years) and 3 (4.8%, 95% CI: 1.0, 13.5%) had enlarged PFNs (median follow up 6.3 years). None of the PFN features, clinical features, nor ancillary information from the CT proved to be statistically significant. CONCLUSIONS: Despite the lack of statistically significant distinguishing features to predict growth, our results are reassuring, since the majority of PFNs in our oncology patients were decreased or unchanged in size which is comparable to previously published data on PFNs in non-oncologic patients. Thus, we can similarly presume these nodules are most likely benign and can provide reassurance to our oncologic colleagues and our patients. Larger studies are warranted to further evaluate PFNs in the oncologic population which also examines the nodules by cancer type.


Subject(s)
Lung Neoplasms/pathology , Solitary Pulmonary Nodule/pathology , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods
12.
Radiology ; 289(2): 546-553, 2018 11.
Article in English | MEDLINE | ID: mdl-30204073

ABSTRACT

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.


Subject(s)
Computed Tomography Angiography/methods , Contrast Media/pharmacokinetics , Iohexol/pharmacokinetics , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Radiographic Image Enhancement/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Iodine/pharmacokinetics , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Young Adult
13.
Ann Thorac Surg ; 106(1): 242-248, 2018 07.
Article in English | MEDLINE | ID: mdl-29534953

ABSTRACT

BACKGROUND: The aim of this study was to assess preoperative computed tomography characteristics of thymic carcinomas and to investigate which features could predict an incomplete surgical resection. A secondary aim was to correlate preoperative imaging features with Masaoka stage. METHODS: In this study, approved by our Institutional Review Board, two readers retrospectively reviewed preoperative computed tomography scans at our tertiary referral oncology center between 1994 and 2014. Imaging features analyzed included tumor morphology, infiltration of surrounding mediastinal fat, loss of surrounding fat plane, degree of contact between tumor and great vessels, and associated pulmonary or pleural abnormality. Surgical and pathologic records were reviewed for completeness of surgical resection and Masaoka stage. RESULTS: Forty-one patients were included, with Masaoka stage I (n = 3), stage II (n = 4), stage III (n = 12), and stage IV (n = 22). Twenty-one patients (51%) had a complete surgical resection. Ten had microscopic residual disease (R1) with involved surgical margins at pathology, and 10 patients had macroscopic residual disease (R2) at surgery. In addition to lesion size, the feature associated with incomplete surgical resection was the degree of tumor contact with adjacent mediastinal vessels on the preoperative computed tomography image (p = 0.038). Many of the more common features associated with incomplete resection were also more likely to be present in patients with late Masaoka stage (III/IV), including infiltration of the mediastinal fat, which was present in all 34 patients with Masaoka stage III/IV compared with 5 patients (71%) with stage I/II (p = 0.03). CONCLUSIONS: Preoperative computed tomography imaging features may help to identify patients at risk for an incomplete surgical resection.


Subject(s)
Thymectomy/methods , Thymoma/diagnostic imaging , Thymoma/surgery , Tomography, X-Ray Computed , Adult , Aged , Cohort Studies , Disease-Free Survival , Female , Humans , Ireland , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Predictive Value of Tests , Preoperative Care/methods , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Thymectomy/mortality , Thymoma/mortality , Thymoma/pathology , Tomography, X-Ray Computed/methods , Treatment Outcome
14.
Cancer ; 124(1): 105-109, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-28940498

ABSTRACT

BACKGROUND: In a phase 1 study of pulse/continuous-dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)-mutant lung cancers with untreated brain metastases. METHODS: Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly. The primary endpoints were the overall and CNS response rates (according to version 1.1 of the Response Evaluation Criteria in Solid Tumors). RESULTS: Between May 2015 and August 2016, 19 patients were enrolled. Forty-two percent of the patients had target brain lesions, and the median size of the target brain lesions was 13 mm. Overall, 14 patients (74%; 95% confidence interval [CI], 51%-89%) had partial responses. The response rate in brain metastases was 75%. The overall median progression-free survival was 10 months (95% CI, 7 months to not reached). Only 3 patients (16%) had CNS progression. To date, 4 patients required CNS radiation at some time during their course. The adverse events (any grade) seen in 10% or more of the patients were rash, diarrhea, nausea, an increase in alanine aminotransferase, and fatigue. CONCLUSIONS: Pulse/continuous-dose erlotinib produced a 74% overall response rate and a 75% response rate in brain metastases in patients with EGFR-mutant lung cancers and untreated brain metastases. CNS control persisted even after progression elsewhere. Although this regimen did not improve progression-free survival or delay the emergence of EGFR T790M, it prevented progression in the brain and could be useful in situations in which CNS control is critical. Cancer 2018;124:105-9. © 2017 American Cancer Society.


Subject(s)
Adenocarcinoma/drug therapy , Brain Neoplasms/drug therapy , Erlotinib Hydrochloride/administration & dosage , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/administration & dosage , Adenocarcinoma/genetics , Adenocarcinoma/radiotherapy , Adenocarcinoma/secondary , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Cranial Irradiation/statistics & numerical data , Disease-Free Survival , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Response Evaluation Criteria in Solid Tumors , Treatment Outcome , Tumor Burden
15.
Clin Imaging ; 39(5): 735-49, 2015.
Article in English | MEDLINE | ID: mdl-26117564

ABSTRACT

UNLABELLED: Lung cancer is the leading cause of cancer-related deaths in the United States. Several surgical techniques are currently used as part of the standard of care for early-stage lung cancer. Differentiating normal postoperative changes from complications is essential in the management of these patients. This article will review the various surgical approaches used, ranging from wedge resection to pneumonectomy, and will outline their expected postsurgical changes. Early and late postsurgical complications will be described, some of which are unique to the type of surgery performed. In addition, local tumor recurrence is a form of postoperative complication and must be distinguished from typical postoperative or postradiation change. Knowledge of both common and uncommon postoperative complications is crucial in the follow-up of lung cancer patients. SUMMARY STATEMENT: Familiarity with the appearance of postoperative complications in lung cancer patients is vital to distinguish it from the normal postoperative or postradiation appearance in follow-up imaging.


Subject(s)
Lung Neoplasms/surgery , Lung/diagnostic imaging , Lung/surgery , Neoplasm Recurrence, Local/diagnostic imaging , Postoperative Complications/diagnostic imaging , Thoracic Surgical Procedures , Humans , Tomography, X-Ray Computed
16.
Clin Imaging ; 39(2): 243-6, 2015.
Article in English | MEDLINE | ID: mdl-25496668

ABSTRACT

OBJECTIVE: The objective of the study was to describe the imaging appearances of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) on computed tomography (CT). MATERIALS AND METHODS: Electronic medical records were searched for patients with pathology-proven DIPNECH who had a CT available for review. Eleven patients were included. RESULTS: The most common finding on CT was small pulmonary nodules which were present in all patients and were multiple (≥5) in 7/11 patients. Other CT findings included mosaic pattern attenuation and bronchial wall thickening/bronchiectasis. CONCLUSION: DIPNECH should be considered as a diagnostic possibility when multiple small pulmonary nodules are identified on CT, particularly if there is an associated carcinoid tumor.


Subject(s)
Carcinoid Tumor/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Multiple Pulmonary Nodules/diagnostic imaging , Neuroendocrine Cells/diagnostic imaging , Precancerous Conditions/diagnostic imaging , Aged , Aged, 80 and over , Female , Humans , Hyperplasia/diagnostic imaging , Middle Aged , Radiography
17.
Surg Oncol Clin N Am ; 23(4): 709-33, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25246047

ABSTRACT

Computed tomography (CT) is the primary imaging modality for the diagnosis, staging, and follow-up of most thoracic cavity tumors. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT has established itself as a supplementary tool to CT in lung cancer staging and in the assessment for distant metastases of many thoracic tumors. Magnetic resonance imaging is an important adjunctive imaging modality in thoracic oncologic imaging and is used as a problem-solving tool to assess for chest wall invasion, intraspinal extension, and cardiac/vascular invasion. Imaging can facilitate minimally invasive biopsy of most thoracic tumors and is vital in the pretreatment planning of radiation therapy.


Subject(s)
Carcinoma/diagnosis , Lung Neoplasms/diagnosis , Magnetic Resonance Imaging , Mediastinal Neoplasms/diagnosis , Pleural Neoplasms/diagnosis , Positron-Emission Tomography , Thymus Neoplasms/diagnosis , Tomography, X-Ray Computed , Early Detection of Cancer , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Radiopharmaceuticals
18.
J Thorac Oncol ; 9(7): 1023-1030, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24926547

ABSTRACT

INTRODUCTION: The aim of the study was to identify preoperative computed tomography (CT) imaging characteristics that correlated with surgical resectability. METHODS: We retrospectively reviewed the CT scans of 133 patients who underwent surgical resection for thymoma at our institution between July 21, 1997, and September 22, 2010. Imaging characteristics recorded included tumor size, attenuation, contact of mediastinal vessels, tumor morphology, infiltration of surrounding fat, changes in the adjacent lung parenchyma, lymphadenopathy, and pleural involvement. RESULTS: The study group included 66 men and 67 women, aged 23-88 years (mean 58.8 years). Eighty patients (60.2%) were Masaoka stage I or II and 53 (39.8%) were Masaoka stage III or IV. Twenty-three patients (17.3%) had an incomplete surgical resection. Of these, 15 patients had microscopic residual disease (11.2%) and eight had gross residual disease (6.0%). The preoperative CT characteristics that correlated with an incomplete surgical resection included a lobulated tumor contour (p = 0.016), greater than or equal 50% abutment of the circumference of an adjacent vessel (p < 0.001), thoracic lymphadenopathy (p = 0.029), adjacent lung changes (p = 0.005) and pleural nodularity (p = 0.001). Tumor size was larger in the incompletely versus completely resected groups, with mean values of 9.7 and 6.9 cm (p value 0.013). On multivariate analysis, only degree of abutment of adjacent vessels and pleural nodularity were independent predictors of incomplete resection. CONCLUSIONS: Preoperative CT findings can predict the likelihood of successful surgical resection and could help to identify patients who might benefit from neoadjuvant chemotherapy.


Subject(s)
Thymoma/diagnostic imaging , Thymoma/surgery , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/surgery , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Pleural Diseases/diagnostic imaging , Predictive Value of Tests , Preoperative Care , Retrospective Studies , Thymectomy , Thymoma/pathology , Thymus Neoplasms/pathology , Tumor Burden , Young Adult
19.
Clin Imaging ; 38(5): 637-40, 2014.
Article in English | MEDLINE | ID: mdl-24928823

ABSTRACT

Our aim was to evaluate clinical management and outcomes in cancer patients who had an indeterminate Computed Tomographic Pulmonary Angiogram (CTPA) for the assessment of pulmonary embolus. We reviewed 1000 CTPA studies and identified 251 limited (indeterminate) CTPA. We examined follow-up imaging and reviewed clinical management decisions and any positive diagnosis of venous thromboembolic disease (VTE) within the subsequent 90 days. 60 patients (23.9%) had a follow-up imaging study within five days. 8 had a positive study for VTE disease within 5 days. 3 patients (1.2%) were placed on anticoagulation therapy based on the limited CT result.


Subject(s)
Angiography/methods , Lung Neoplasms/diagnostic imaging , Multidetector Computed Tomography/methods , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Lung/diagnostic imaging , Lung Neoplasms/complications , Male , Middle Aged , Pulmonary Embolism/etiology , Reproducibility of Results , Young Adult
20.
J Am Coll Radiol ; 11(8): 791-5, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24818987

ABSTRACT

PURPOSE: An integral part of realizing the enormous potential of imaging in patient care is close communication between radiologists and referring physicians. One key element of this process is the communication of unexpected significant findings. The authors examined the performance of a PACS-based alert system in the appropriate communication of reports containing unexpected significant findings to referring physicians. METHODS: A PACS-integrated key word system was developed such that an e-mail was sent to the referring clinician if a radiologist detected a significant unexpected finding. The number, source, and outcome of chest radiographic unexpected findings over a 14-month period were analyzed. The time for response of the referring physician plus time for follow-up were also examined. RESULTS: Key words were applied to 158 of the 39,665 chest radiographs (0.4%) obtained during the study period. The emergency department was the most frequent referral location (46.2%). Final diagnostic categories included malignancy (13.9%), benign lesion (49.4%), and no abnormality (20.2%). The average time to acknowledgment by clinicians of notification was 3.1 days, although 57.6% were acknowledged within 24 hours. The mean time interval to the next relevant radiologic investigation was 26 days among the 77.8% of findings that underwent radiologic follow-up. CONCLUSIONS: The development of electronic alert systems, which are integrated into PACS, can aid greatly in report communication and eliminate the risk associated with unread reports that contain significant or unexpected findings.


Subject(s)
Electronic Mail , Interdisciplinary Communication , Lung Neoplasms/diagnostic imaging , Radiography, Thoracic , Radiology Information Systems/organization & administration , Diagnosis, Differential , Humans , Quality Assurance, Health Care , Referral and Consultation/organization & administration
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