Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

Background: The strategy of dual blockade of TGF-ß and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFß1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

Ultrasound, CT and MRI Appearances of a Rare Symptomatic Laryngeal Chondrometaplasia: A Case Report.

Symptomatic laryngeal chondrometaplasia is rare. To the best of our knowledge, there are only few case reports on laryngeal chondrometaplasia. The imaging appearance of this uncommon disease is even more rarely described. There are only two case reports describing its appearances in computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound (US) features have not been reported so far. This case report is to show the US, CT and MRI features of this disease entity to stress the role of imaging in this disease.

Ultrasound elastography in the head and neck. Part I. Basic principles and practical aspects.

Ultrasound elastography (USE) is a rapidly developing field of imaging that measures and displays tissue elasticity or stiffness properties using ultrasound. In recent years, real-time USE modes have appeared on commercially available clinical ultrasound machines, stimulating an explosion of research into potential oncologic and non-oncologic clinical applications of USE. Preliminary evidence suggests that USE can differentiate benign and malignant conditions accurately in several different tissues. This article presents an overview of the basic principles of different USE technologies that are currently under investigation in the head and neck region. In addition, more practical aspects pertaining to the optimal performance of USE at this site are discussed.

Ultrasound elastography in the head and neck. Part II. Accuracy for malignancy.

Ultrasound elastography (USE) describes a variety of ultrasound-based imaging techniques that measure tissue stiffness properties, and is currently under intense investigation for tissue characterization in several anatomic sites. This article summarizes the evidence regarding the accuracy of USE for malignancy in the head and neck. Currently, most published data pertains to small pilot studies with varied methodologies. Encouragingly, most studies have documented promising results for USE in terms of high accuracy for malignancy in thyroid nodules and cervical lymph nodes, which have surpassed conventional sonographic criteria. However, a minority of studies have documented opposite findings. USE seems to be suboptimal for salivary malignancies, and some evidence suggests that USE does not provide useful diagnostic information compared with conventional ultrasonography for miscellaneous neck masses. Further larger studies are required to validate these findings although, in view of the predominance of highly optimistic results for thyroid nodules and cervical lymph nodes, USE may become a useful ancillary technique in the routine diagnostic work-up of lesions in these tissues in the near future.

MR elastography of the head and neck: driver design and initial results.

PURPOSE: The purpose was to describe the design and fabrication of a driver suitable for magnetic resonance elastography (MRE) of the head and neck and to assess its performance in evaluating human parotid gland, lymph nodes and thyroid at 3.0 T. MATERIALS AND METHODS: A head and neck driver was fabricated using a commercial transducer, headrest mould and piston extension. Driver performance was tested using a motion-sensitized spin-echo MRE pulse sequence. Six healthy volunteers and three patients (two metastatic nodes and one papillary carcinoma) were evaluated using MRE. Viscoelastic maps were computed to obtain storage modulus (G') and loss modulus (G") of the normal parotid and thyroid, metastatic node and thyroid cancer. Reproducibility was assessed by coefficient of variation. RESULTS: All subjects completed MRE examination without discomfort. Initial G' and G" values were as follows: normal parotid gland, 1.12 kPa and 0.48 kPa; thyroid, 0.58 kPa and 0.42 kPa; metastatic node, 0.66 kPa and 0.58 kPa; and thyroid cancer, 0.17 kPa and 0.28 kPa. Based on parotid data, the coefficient of variation for G' and G" was 4.7% and 9.8%. CONCLUSION: A new MRE driver for head and neck was successfully implemented, and our initial results suggested the device was suitable for the mechanical assessment of tissues in the head and neck.

Shear wave elastography of thyroid nodules in routine clinical practice: preliminary observations and utility for detecting malignancy.

OBJECTIVE: To evaluate real-time shear wave ultrasound elastography (SWE) for characterizing focal thyroid lesions in routine clinical practice. METHODS: Seventy-four patients with 81 focal thyroid lesions undergoing conventional US with needle cytology also underwent SWE. Absolute and relative SWE stiffness measurements on colour-coded elastograms were correlated with cytology and their discriminatory performances assessed. RESULTS: Seventeen nodules were malignant (13 papillary, 4 other cancers), 45 benign (43 hyperplastic nodules, 2 focal thyroiditis), 5 indeterminate ("follicular lesions"), and 5 had inadequate cytology. SWE results were higher in malignant than benign nodules (P values 0.02-0.05) although their discriminatory performances were mediocre (AUCs 0.58-0.74). The most accurate SWE cut-off, 34.5 kPa for a 2-mm region of interest, achieved 76.9 % sensitivity and 71.1 % specificity for discriminating papillary cancer from benign nodules. No thresholds produced high sensitivity without lowering specificity appreciably, and vice versa. Nodule size correlated with SWE for benign nodules (P < 0.01). Intranodular cystic change or calcification did not influence SWE. Qualitatively, elastographic artefacts and foci lacking colour elasticity signal occurred in some solid nodules. CONCLUSION: Although malignant nodules are generally stiffer than benign nodules, the precision results do not suggest a definitive role for SWE, at present, in identifying or excluding thyroid malignancy. KEY POINTS : • Shear wave ultrasound elastography (SWE) offers new insight into thyroid disease. • Papillary cancers have higher SWE indices (equating to higher stiffness) than benign nodules. • SWE appears limited in terms of identifying or excluding thyroid malignancy accurately. • Vertically aligned elastographic artefacts can occur in thyroid SWE. • Areas lacking SWE colour signal can occur in some solid thyroid nodules.

A pilot study evaluating real-time shear wave ultrasound elastography of miscellaneous non-nodal neck masses in a routine head and neck ultrasound clinic.

A pilot study was performed to evaluate shear wave ultrasound elastography (SWE) for miscellaneous non-nodal/salivary/thyroid neck lesions. Forty-six lesions undergoing conventional sonography also underwent SWE. Elastic moduli from the stiffest areas in lesions were correlated with diagnosis. Forty lesions were benign (9 lipomas, 8 lymphatic/venous vascular malformations, 7 thyroglossal duct cysts, 4 branchial cleft cysts, 4 abscesses/phlegmons, 3 neurogenic tumors and 1 each of paraganglioma, sebaceous cyst, pseudotumor, hypertrophic scar, ranula) and 6 were malignant (1 malignant fibrous histiocytoma, 2 primary squamous cell carcinomas and 3 intramuscular metastases [2 squamous cell carcinomas, 1 malignant melanoma]).Median stiffness of malignant lesions (226.4 kPa, range 55.6 to 300.0) was higher than benign lesions (28.3 kPa, range 4.0 to 300.0) (p < 0.001). SWE cut-off with highest accuracy (174.4 kPa) achieved 83.3% sensitivity and 97.5% specificity, and the cut-off with 100% sensitivity (55.6 kPa) achieved 75% specificity. All malignant lesions were suspected on conventional sonography. The preliminary data indicate that SWE is feasible for miscellaneous neck lesions. SWE would not have altered management in terms of detecting undisclosed malignancies, although as a quantitative technique, it may increase the diagnostic confidence of less experienced operators performing head and neck ultrasound.

Shear wave elastography of focal salivary gland lesions: preliminary experience in a routine head and neck US clinic.

OBJECTIVES: To evaluate shear wave elastography (SWE) for focal lesions in major salivary glands. METHODS: Sixty lesions (49 parotid, 11 submandibular) undergoing routine ultrasound (grey scale and Doppler) also underwent SWE before US-guided needle aspiration for cytology. Quantitative indices of the shear elastic modulus (stiffness) were compared with cytological results. RESULTS: Fifty-five lesions were benign (21 pleomorphic adenomas, 18 Warthin's tumours; 16 others) and 5 malignant (2 mucoepidermoid carcinomas, 1 myoepithelial carcinoma, 1 B-cell lymphoma, 1 nodal metastasis). Shear modulus of benign lesions, median 18.3 kPa, overlapped appreciably with malignant lesions, median 13.5 kPa. However, 2 mucoepidermoid carcinomas had the highest stiffness values (81.9 kPa, 132.0 kPa). Stiffness of pleomorphic adenomas (median 22.5 kPa) was higher than Warthin's tumours (16.9 kPa) (P = 0.05 Mann-Whitney U-test). The standard deviation of stiffness values within a lesion, used as an indicator of spatial heterogeneity, was highest in mucoepidermoid cancers (median 44.2 kPa), followed by pleomorphic adenomas (median 12.4 kPa) and remaining lesions (medians 1.4-10.3 kPa). CONCLUSION: This study shows a degree of clustering of SWE indices according to pathology although it appears that SWE has suboptimal performance for ruling out malignancy, thus limiting its use in routine practice. KEY POINTS: • Shear wave elastography is a feasible technique for focal salivary gland lesions. • Elastographic artefacts aggravated by the regional anatomy may hinder this technique. • Elastographic indices vary according to pathology but there is appreciable overlap. • Overlapping indices for malignant and benign lesions limit its utility. • Pleomorphic adenomas have higher elasticity indices, i.e. are stiffer, than Warthin's tumours.

Current role of radionuclide imaging in differentiated thyroid cancer.

Nuclear medicine plays an integral role in the management of differentiated thyroid cancer. This editorial aims to provide a summary of the current role of radionuclide imaging, including whole body iodine scan and fluorodeoxyglucose (FDG)-positron emission tomography (PET), in the diagnostic work-up and follow-up of patients with thyroid cancer.

Malignant cervical lymphadenopathy: diagnostic accuracy of diffusion-weighted MR imaging.

PURPOSE: To prospectively determine the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging for discrimination of malignant neck nodes due to lymphoma, squamous cell carcinoma (SCC), and undifferentiated nasopharyngeal carcinoma (NPC), with histologic findings and imaging criteria as reference standards. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Patients with malignant lymphadenopathy underwent 1.5-T diffusion-weighted MR imaging. A region of interest was drawn around the malignant node on apparent diffusion coefficient (ADC) maps; ADC values were compared (Kruskal-Wallis test). Receiver operating characteristic analysis was employed to investigate whether ADC values could aid in discrimination among malignancies. RESULTS: Forty-three patients (34 men, nine women; mean age, 54 years) with 43 nodes underwent imaging. Mean ADC values for lymphoma (n = 8), NPC (n = 17), and SCC (n = 18) were (0.664 +/- 0.071 [standard deviation]) x 10(-3) mm(2)/sec, (0.802 +/- 0.128) x 10(-3) mm(2)/sec, and (1.057 +/- 0.169) x 10(-3) mm(2)/sec, respectively, with significant differences between SCC and lymphoma or NPC (P < .001) and between NPC and lymphoma (P = .04). To optimize sensitivity and specificity with equal weighting, ADC threshold values for distinguishing between SCC and NPC, between SCC and lymphoma, and between NPC and lymphoma were 0.894 x 10(-3) mm(2)/sec, 0.824 x 10(-3) mm(2)/sec, and 0.694 x 10(-3) mm(2)/sec, respectively. To produce a 100% specificity while sensitivity is maximized, the following ADC threshold values were obtained for prediction of differentiation between malignancies: (a) SCC versus lymphoma, greater than 0.824 x 10(-3) mm(2)/sec (sensitivity, 94%), and lymphoma versus SCC, less than 0.767 x 10(-3) mm(2)/sec (sensitivity 88%); (b) NPC versus SCC, less than 0.764 x 10(-3) mm(2)/sec (sensitivity, 47%), and SCC versus NPC, greater than 1.093 x 10(-3) mm(2)/sec (sensitivity, 39%); (c) NPC versus lymphoma, greater than 0.788 x 10(-3) mm(2)/sec (sensitivity, 53%), and lymphoma versus NPC, no suitable threshold value. CONCLUSION: Diffusion-weighted MR imaging shows significant differences among malignant nodes of SCC, lymphoma, and NPC. ADC threshold values can help distinguish SCC from lymphoma. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2451061804/DC1.

Sequential chemotherapy with combination irinotecan and cisplatin followed by docetaxel for treatment-naïve patients with advanced non-small cell lung cancer.

BACKGROUND: Sequential administration of platinum-based doublet therapy and then a taxane may reduce the risk of drug resistance and, therefore, improve treatment outcome. This study was designed to evaluate the efficacy and tolerability of sequential administration of irinotecan and cisplatin and then docetaxel in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Eligible patients received irinotecan in 60-mg/m2 infusions for 30 to 60 minutes on days 1, 8, and 15, and cisplatin in 75-mg/m2 infusions for 60 minutes on day 1 every 28 days for four cycles (IC). Regardless of the response, patients received up to four cycles of sequential docetaxel in 75-mg/m2 infusions for 60 minutes. RESULTS: Forty-six patients with histologically confirmed chemotherapy-naïve stage IIIB or IV NSCLC were enrolled, of whom 42 were evaluable. The response rate at completion of chemotherapy with IC was 45.2% (95% confidence interval [CI]: 30.2%-60.3%). Five patients had improvement of disease status during sequential docetaxel, and seven patients had disease progression. Progression-free survival was 8.0 months (95% CI: 5.4-9.9 months), and the overall median survival was 14.6 months (95% CI: 9.8-17.9 months). The 1-, 2-, and 3-year survival rates were 54.3%, 22.6%, and 12.1%, respectively. The incidence of severe (> or =CTC V2 grade 3) neutropenia during IC was 23.9% compared with 95.7% for sequential docetaxel (p < 0.0001). CONCLUSION: Sequential administration of IC and then docetaxel is feasible and is associated with a prolonged progression-free survival, but the current data do not confirm an improvement in treatment outcome by the sequential approach.