Treatment Response and Clinical Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors to Lutetium-177-DOTATATE.

INTRODUCTION: Lutetium-177 (177Lu)-DOTATATE received FDA approval in 2018 to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs). Little data are available on response and outcomes for well-differentiated (WD) high-grade (HG) NETs treated with 177Lu-DOTATATE. MATERIALS AND METHODS: Patients with WD HG NETs treated with 177Lu-DOTATATE at MSK from 2018 to 2020 were identified. Demographics, response (RECIST 1.1), and progression-free survival (PFS) were determined. Next-generation sequencing (NGS) was performed in the archival tumor. RESULTS: Nineteen patients, all with progressive, heavily treated disease, were identified. Sites of tumor origin were: pancreas (74%), small bowel (11%), rectum (11%), and lung (5%); median Ki-67 was 32% (range 22-56). Thirteen patients (68%) completed all four 177Lu-DOTATATE cycles. Best response (N = 18 evaluable) was: 5/18 (28%) partial response, 8/18 (44%) stable disease, and 5/18 (28%) disease progression. Median PFS was 13.1 months (95% CI: 8.7-20.9). Most common treatment-related toxicities were thrombocytopenia (9 patients, 47%; G3/4, 1 patient, 5%), anemia (7 patients, 37%; G3/4, 2 patients, 11%), leukopenia (6 patients, 32%; G3/4, 0 patients), and liver function test elevation (4 patients, 21%; G3/4, 0 patients). NGS results were available from 13/19 tumors (68%). The most observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations identified. CONCLUSION: We observed a meaningful disease control rate of 72% during treatment of WD HG NETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of patients received all four treatment cycles with toxicities largely bone marrow-related. As would be expected in WD NETs, the vast majority had alterations in chromatin remodeling genes and no RB1 alterations.

Potential of right to left ventricular volume ratio measured on chest CT for the prediction of pulmonary hypertension: correlation with pulmonary arterial systolic pressure estimated by echocardiography.

OBJECTIVES: To investigate the correlation of right ventricular (RV) to left ventricular (LV) volume ratio measured by chest CT with pulmonary arterial systolic pressure (PASP) estimated by echocardiography. METHODS: 104 patients (72.47 ± 13.64 years; 39 male) who had undergone chest CT and echocardiography were divided into two groups (hypertensive and normotensive) based upon an echocardiography-derived PASP of 25 mmHg. RV to LV volume ratios (RV(V)/LV(V)) were calculated. RV(V)/LV(V) was then correlated with PASP using regression analysis. The Area Under the Curve (AUC) for predicting pulmonary hypertension on chest CT was calculated. RESULTS: In the hypertensive group, the mean PASP was 46.29 ± 14.42 mmHg (29-98 mmHg) and there was strong correlation between the RV(V)/LV(V) and PASP (R = 0.82, p < 0.001). The intraobserver and interobserver correlation coefficients for RV(V)/LV(V) were 0.990 and 0.892. RV(V)/LV(V) was 1.01 ± 0.44 (0.51-2.77) in the hypertensive and 0.72 ± 0.14 (0.52-1.11) in the normotensive group (P <0.05). With 0.9 as the cutoff for RV(V)/LV(V), sensitivity and specificity for predicting pulmonary hypertension over 40 mmHg were 79.5 % and 90 %, respectively. The AUC for predicting pulmonary hypertension was 0.87 CONCLUSION: RV/LV volume ratios on chest CT correlate well with PASP estimated by echocardiography and can be used to predict pulmonary hypertension over 40 mmHg with high sensitivity and specificity.

TriDFusion (3DF) image viewer.

BACKGROUND: An open-source, extensible medical viewing platform is described, called the TriDFusion image viewer (3DF). The 3DF addresses many broad unmet needs in nuclear medicine research; it provides a viewer with several tools not available in commercial nuclear medicine workstations, yet invaluable for imaging in research studies. RESULTS: The 3DF includes an image integration platform to register images from multiple imaging modalities together with delineated volumes of interest (VOIs), structures and dose distributions. It can process images from different vendors' systems and is therefore vendor neutral. The 3DF also provides a convenient tool for performing multi-modality image analysis and fusion. The functional components currently being distributed is open-source code that includes: (1) a high quality viewer that can display axial, coronal, and sagittal tomographic images, maximum intensity projection images, structure contours, and isointensity contour lines or dose colorwash, (2) multi-image fusion allowing multiple images to be fused with VOI and dose distributions, (3) a suite of segmentation tools to edit and/or create tumor and organ VOIs, (4) dosimetry tools for several radioisotopes, (5) clinical tools for correcting acquisition errors, including patient orientation, and (6) the ability to save the resultant image and VOI as DICOM files or to export the numerical results as comma separated values files. Because the code is written in MATLAB™, it is highly readable and is easier for the coder to make changes compared to languages such as C or C++. In what follows, we describe the content of the new TriDFusion (3DF) image viewer software platform using examples of a number of clinical research workflows. Such examples vary in complexity but illustrate the main attributes of the software. CONCLUSIONS: In summary, 3DF provides a powerful, convenient, easy-to-use suite of open-source imaging research tools for the nuclear medicine community that allows physicians, medical physicists, and academic researchers to display, manipulate, and analyze images.

The Quest for an Accurate Functional Tumor Volume with 68Ga-DOTATATE PET/CT.

68Ga-labeled somatostatin analog (SSA) PET/CT is now a standard-of-care component in the management of neuroendocrine tumors (NETs). However, treatment response for NETs is still assessed with morphologic size measurements from other modalities, which can result in inaccuracy about the disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared with morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. Methods: The clinical and imaging data of 327 NET patients were collected at Memorial Sloan Kettering Cancer Center between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 wk and were excluded if they had any intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated SSA. Lesions were excluded if they contained necrotic components or were lobulated. This exclusion resulted in 94 lesions in 20 patients. The FTV for each lesion was evaluated with a hand-drawn assessment and 3 automated techniques: 50% threshold from SUVmax, 42% threshold from SUVmax, and background-subtracted lesion activity. These measurements were compared with volume calculated from morphologic volume measurements. Results: The FTV calculation methods showed varying correlations with morphologic volume measurements. FTV using a 42% threshold had a 0.706 correlation, hand-drawn volume from PET imaging had a 0.657 correlation, FTV using a 50% threshold had a 0.645 correlation, and background-subtracted lesion activity had a 0.596 correlation. The Bland-Altman plots indicated that all FTV methods had a positive mean difference from morphologic volume, with a 50% threshold showing the smallest mean difference. Conclusion: FTV determined with thresholding of SUVmax demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method was more accurate than FTV calculated from hand-drawn volume assessments. Threshold-based automated FTV assessment promises to better determine disease extent and prognosis in patients with NETs.

A trial of drug-induced sleep endoscopy in the surgical management of sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: To determine the reliability and validity of drug-induced sleep endoscopy (DISE) for patients undergoing surgery for sleep-disordered breathing (SDB). STUDY DESIGN: Non-randomized, prospective clinical trial. METHODS: Patients with sleep-disordered breathing were evaluated for multi-level upper airway surgery by awake and drug-induced sleep endoscopy to identify levels and degree of airway collapse. The reliability of a drug-induced sleep endoscopy rating index was assessed by comparing scores of three blinded investigators. The validity was assessed by comparison of drug-induced sleep endoscopy index scores from awake and drug-induced sleep endoscopy; correlation between drug-induced sleep endoscopy scores and Apnea-Hypopnea Index; and determination whether drug-induced sleep endoscopy affected the original surgical plan. RESULTS: Thirty-eight patients (22 M, 16 F) underwent preoperative assessment with awake and drug-induced sleep endoscopy. Drug-induced sleep endoscopy was successfully performed in all but one patient (97%) who became combative during propofol infusion. Using an internal airway grading scale, drug-induced sleep endoscopy demonstrated more severity of collapse than awake endoscopy (P = 0.0001). The surgical plan was changed after drug-induced sleep endoscopy in 23 (62%) cases and unchanged in 14 (38%). The majority (73%) had multi-segmental airway collapse with fewer having single-level palatal (16%) or tongue base (11%) collapse. Scoring of drug-induced sleep endoscopy videos demonstrated good intrarater (κ 0.61) and interrater (κ 0.65) correlation. CONCLUSIONS: Drug-induced sleep endoscopy provides more clinical information to assess airway function and collapse than awake endoscopy alone and assists in the surgical planning. Additional investigation is needed to standardize drug-induced sleep endoscopy techniques, training, and interpretation.

Image quality and radiation dose of low dose coronary CT angiography in obese patients: sinogram affirmed iterative reconstruction versus filtered back projection.

PURPOSE: To investigate the image quality and radiation dose of low radiation dose CT coronary angiography (CTCA) using sinogram affirmed iterative reconstruction (SAFIRE) compared with standard dose CTCA using filtered back-projection (FBP) in obese patients. MATERIALS AND METHODS: Seventy-eight consecutive obese patients were randomized into two groups and scanned using a prospectively ECG-triggered step-and-shot (SAS) CTCA protocol on a dual-source CT scanner. Thirty-nine patients (protocol A) were examined using a routine radiation dose protocol at 120 kV and images were reconstructed with FBP (protocol A). Thirty-nine patients (protocol B) were examined using a low dose protocol at 100 kV and images were reconstructed with SAFIRE. Two blinded observers independently assessed the image quality of each coronary segment using a 4-point scale (1=non-diagnostic, 4=excellent) and measured the objective parameters image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Radiation dose was calculated. RESULTS: The coronary artery image quality scores, image noise, SNR and CNR were not significantly different between protocols A and B (all p>0.05), with image quality scores of 3.51±0.70 versus 3.55±0.47, respectively. The effective radiation dose was significantly lower in protocol B (4.41±0.83 mSv) than that in protocol A (8.83±1.74 mSv, p<0.01). CONCLUSION: Compared with standard dose CTCA using FBP, low dose CTCA using SAFIRE can maintain diagnostic image quality with 50% reduction of radiation dose.