rearrangements are an established targetable oncogenic driver in non-small cell lung cancer (NSCLC). The goal of this study was to determine the imaging features of the primary tumor and metastatic ...patterns in advanced
-rearranged (
+) NSCLC that may be different from those in
-mutant (
+) or
wild-type (
-/
-) NSCLC.
Patients with advanced
+,
+, or
NSCLC were retrospectively identified. Two radiologists concurrently assessed the imaging features of the primary tumor and the distribution of metastases in these patients.
We identified a cohort of 333 patients with metastatic NSCLC (119
cases, 116
cases, and 98
-/
- cases). Compared with
+ and
-/
- NSCLC, the primary tumor in
+ NSCLC was more likely to be located in the lower lobes (53% of
, 34% of
, and 36% of
-/
- tumors;
< 0.05), less likely to be subsolid (1% of
+, 11% of
, and 8% of
-/
- tumors;
< 0.02), and less likely to have air bronchograms (7% of
, 28% of
, and 29% of
-/
- tumors;
< 0.01). Compared with
+ and
-/
- tumors,
+ tumors had higher frequencies of distant nodal metastasis (20% of
tumors vs 2% of
and 9% of
-/
- tumors;
< 0.05) and lymphangitic carcinomatosis (37% of
tumors vs 12% of
and 12% of
-/
- tumors;
< 0.01), but
+ tumors had a lower frequency of brain metastasis compared with
+ tumors (24% vs 41%;
= 0.01). Although there was no statistically significant difference in the frequencies of bone metastasis among the three groups, sclerotic bone metastases were more common in the
+ tumors (22% vs 7% of
tumors and 6% of
-/
- tumors;
< 0.01).
Advanced
+ NSCLC has primary tumor imaging features and patterns of metastasis that are different from those of
+ or
-/
- wild type NSCLC at the time of initial presentation.
Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust ...CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases.
In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as ≥1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.
Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval CI: 44.9%–92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%–100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months–not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%–90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%–100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months–not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy.
Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases.
Diffuse Pulmonary Hemorrhage: Clues to the Diagnosis Lichtenberger, John P., MD; Digumarthy, Subba R., MD; Abbott, Gerald F., MD ...
Current problems in diagnostic radiology,
05/2014, Letnik:
43, Številka:
3
Journal Article
Recenzirano
Diffuse pulmonary hemorrhage (DPH) refers to an uncommon but significant condition of bleeding into the alveolar space. Anemia and hemoptysis are important clinical features, but they may be absent. ...Although the radiographic and computed tomography findings are often varied and nonspecific, the imaging manifestations of pulmonary hemorrhage and the associated findings in the thorax often provide important diagnostic information that may lead to a specific diagnosis. DPH significantly influences patient management and has important prognostic implications. This review article explores the imaging findings in DPH and its differential diagnosis, highlighting important clues to this diagnosis and to its underlying etiology. DPH is an uncommon condition characterized by bleeding into the alveolar space that, when recognized on imaging, provides important diagnostic and prognostic information.
Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint ...inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of inducible components of the immunoproteasome and response and (3) a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint blockade. Taken together, results from this cohort demonstrate the complexity of biological determinants underlying immunotherapy outcomes and reinforce the discovery potential of integrative analysis within large, well-curated, cancer-specific cohorts.
The purpose of our study was to determine accuracy of CT texture analysis (CTTA) for differentiating benign from malignant pulmonary nodules, and well-differentiated from poorly differentiated lung ...cancers, with histology as the standard of reference.In this IRB-approved study, 175 adult patients (average age 66 ± 12 years; age range 27-89 years, male 82: female 93) who underwent a noncontrast chest CT examination prior to CT-guided biopsy of pulmonary nodules were included. There were 57 benign (24 tumors or tumor-like lesions; 33 inflammatory conditions) and 120 malignant (29 well-differentiated adenocarcinomas, 48 poorly differentiated adenocarcinomas, and 43 squamous cell carcinomas) diagnoses on pathology. CTTA was performed on the prebiopsy noncontrast CT images using a commercially available software (TexRAD limited, UK). The CTCA features analyzed included mean HU values, percent positive pixels (PPP), mean value of positive pixels (MPP), standard deviation (SD), normalized SD, skewness, kurtosis, and entropy.The ROC analyses showed that normalized SD AUC: 0.63, (CI: 0.55-72), P = .003 had moderate accuracy for differentiating between benign and malignant lesions. For differentiating among well-differentiated and poorly differentiated tumors, the ROC analysis showed that except skewness all other parameters were statistically significant The AUC values of other CTTA parameters were: mean (AUC: 0.73-0.76, P = .001- < .0001).CT texture analyses can reliably predict well- and poorly differentiated lung malignancies. However, inflammatory lung lesions with tissue heterogeneity negatively affect the performance of CTTA when it comes to differentiation between benign and malignant pulmonary nodules.
Purpose
To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in ...primary abdominal malignancies.
Methods
This retrospective IRB-approved study included 18F-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and 18F-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated.
Results
A total of 505 nodules (mean 4 mm, range 1–23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively,
p
< 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients’ management.
Conclusions
Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.
Spontaneous chylous effusions are rare; however, they have been observed by independent investigators in patients treated with RET tyrosine kinase inhibitors (TKIs).
This multicenter, retrospective ...study evaluated the frequency of chylous effusions in patients treated with RET TKIs. Clinicopathologic features and management of patients with chylous effusions were evaluated.
A pan-cancer cohort of 7517 patients treated with one or more multikinase inhibitor or selective RET TKI and a selective TKI cohort of 96 patients treated with selpercatinib or pralsetinib were analyzed. Chylous effusions were most common with selpercatinib (7%), followed by agerafenib (4%), cabozantinib (0.3%), and lenvatinib (0.02%); none were observed with pralsetinib. Overall, 12 patients had chylothorax, five had chylous ascites, and five had both. Time from TKI initiation to diagnosis ranged from 0.5 to 50 months. Median fluid triglyceride level was lower in chylothoraces than in chylous ascites (397 mg/dL interquartile range: 304–4000 versus 3786 mg/dL interquartile range: 842–6596, p = 0.035). Malignant cells were present in 13% (3 of 22) of effusions. Chyle leak was not identified by lymphangiography. After initial drainage, 76% of patients with chylothorax and 80% with chylous ascites required additional interventions. Selpercatinib dose reduction and discontinuation rates in those with chylous effusions were 47% and 0%, respectively. Median time from diagnosis to disease progression was not reached (95% confidence interval: 14.5–undefined); median time from diagnosis to TKI discontinuation was 11.4 months (95% confidence interval: 8.2–14.9).
Chylous effusions can emerge during treatment with selected RET TKIs. Recognition of this side effect is key to prevent potential misattribution of worsening effusions to progressive malignancy.
The second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib recently showed superior efficacy compared to the first-generation ALK inhibitor crizotinib in advanced ALK-rearranged ...NSCLC, establishing alectinib as the new standard first-line therapy. Brigatinib, another second-generation ALK inhibitor, has shown substantial activity in patients with crizotinib-refractory ALK-positive NSCLC; however, its activity in the alectinib-refractory setting is unknown.
A multicenter, retrospective study was performed at three institutions. Patients were eligible if they had advanced, alectinib-refractory ALK-positive NSCLC and were treated with brigatinib. Medical records were reviewed to determine clinical outcomes.
Twenty-two patients were eligible for this study. Confirmed objective responses to brigatinib were observed in 3 of 18 patients (17%) with measurable disease. Nine patients (50%) had stable disease on brigatinib. The median progression-free survival was 4.4 months (95% confidence interval CI: 1.8–5.6 months) with a median duration of treatment of 5.7 months (95% CI: 1.8–6.2 months). Among 9 patients in this study who underwent post-alectinib/pre-brigatinib biopsies, 5 had an ALK I1171X or V1180L resistance mutation; of these, 1 had a confirmed partial response and 3 had stable disease on brigatinib. One patient had an ALK G1202R mutation in a post-alectinib/pre-brigatinib biopsy, and had progressive disease as the best overall response to brigatinib.
Brigatinib has limited clinical activity in alectinib-refractory ALK-positive NSCLC. Additional studies are needed to establish biomarkers of response to brigatinib and to identify effective therapeutic options for alectinib-resistant ALK-positive NSCLC patients.
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