External Validation of a Clinical Score for Patients With Neuroendocrine Tumors Under Consideration for Peptide Receptor Radionuclide Therapy.

Importance: Despite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined. Objective: To assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs. Design, Setting, and Participants: This multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021. Exposures: PRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide. Main Outcomes and Measures: The primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes. Results: A total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36). Conclusions and Relevance: Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT.

A clinical score for neuroendocrine tumor patients under consideration for Lu-177-DOTATATE therapy.

We developed a clinical score (CS) at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with progressive well-differentiated neuroendocrine tumors (NETs) receiving therapy with Lutetium-177 (177Lu)-DOTATATE. Patients under consideration for 177Lu-DOTATATE between March 1, 2016 and March 17, 2020 at VICC were assigned a CS prospectively. The CS included 5 categories: available treatments for tumor type outside of 177Lu-DOTATATE, prior systemic treatments, patient symptoms, tumor burden in critical organs and presence of peritoneal carcinomatosis. The primary outcome of the analysis was progression-free survival (PFS). To evaluate the effect of the CS on PFS, a multivariable Cox regression analysis was performed adjusting for tumor grade, primary tumor location, and the interaction between 177Lu-DOTATATE doses received (zero, 1-2, 3-4) and CS. A total of 91 patients and 31 patients received 3-4 doses and zero doses of 177Lu-DOTATATE, respectively. On multivariable analysis, in patients treated with 3-4 doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated hazard ratio (HR) for PFS was 2.0 (95% CI 1.61-2.48). On multivariable analysis, in patients who received zero doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated HR for PFS was 1.22 (95% CI 0.91-1.65). Among patients treated with 3-4 doses of 177Lu-DOTATATE, those with lower CS experienced improved PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive 177Lu-DOTATATE, suggesting the predictive utility of the score.

Design, Implementation, and Evaluation of a Diversity Program for Radiology.

RATIONALE AND OBJECTIVES: Diagnostic radiology training programs are less diverse than graduating US medical school classes and the patient populations they serve. Inclusion of physicians who are underrepresented minorities in medicine (URMM) can strengthen the profession and help to meet the needs of an increasingly diverse population. Our Department of Radiology developed and implemented a plan to increase the number of URMMs in our residency applicant pool and residency training program. MATERIALS AND METHODS: We designed a recruitment strategy to diversify the radiology residency applicant pool. This included website development, advertising, early exposure opportunities, travel to predominantly minority institutions and national meetings, and mentoring URMM medical students. We implemented parallel activities to increase the number of URMMs in our residency program. These included holistic screening tools for residency application review, a diverse residency recruitment committee, a welcome environment for visiting candidates, and "Second Look Weekend" visits for talented candidates. Primary outcomes measured include change in percentages of URMM applicants in our applicant pool and URMM residents in our residency program. RESULTS: The percentage of URMM radiology residency applicants increased from 7.5% (42 of 556) of the total applicant pool in the 2012 to 2013 recruitment year to 12.6% (98 of 777) in the 2017 to 2018 recruitment year (P = .001). URMM radiology residency representation increased from 0% (0 of 32) in the 2013 to 2014 academic year to 20% (6 of 30) in the 2018 to 2019 academic year (P = .01). CONCLUSION: An intentional, strategic diversity program can diversify an institution's residency applicant pool and increase representation of URMMs in a diagnostic radiology residency program.

ACR Practice Parameter for the Performance of Gallium-68 DOTATATE PET/CT for Neuroendocrine Tumors.

Radiopharmaceuticals targeting cell surface expression of somatostatin receptors (SSTRs) are particularly useful in the evaluation of neuroendocrine tumors. Gallium-68 DOTA-Tyr-octreotatate (Ga-DOTATATE) primarily binds to SSTR type 2 receptors. Ga DOTATATE PET/CT is proven to have high impact on the management of neuroendocrine patients compared to traditional anatomical imaging as well as provides additional information over that of conventional nuclear medicine studies (indium-III DTPA-octreotide). It can result in change in management of approximately 75% of patients with neuroendocrine tumors. Ga DOTATATE and F FDG PET/CT imaging are complementary, with the degree of uptake varying depending on the degree of differentiation of the tumor. Well-differentiated tumors maintain their SSTRs and are positive on Ga DOTATATE PET/CT scan, while dedifferentiated tumors are less likely to demonstrate uptake of Ga DOTATATE but will demonstrate uptake with F FDG PET/CT. In addition, Ga DOTATATE PET/CT identifies patients with SSTR expression in their tumors, who have progressed on somatostatin analog therapy, for treatment with Lu DOTATATE.

Increased renal cyst density on abdominal CT at 100-kVp compared with 120-kVp: a preliminary evaluation.

OBJECTIVE: To compare the radiographic density of renal cysts on contrast-enhanced computed tomography (CT) scans performed at tube voltages of 100 versus 120 kVp. METHODS: Thirty-six renal cysts from contrast-enhanced CT performed on 21 subjects at both 120 kVp and 100 kVp were compared by Kolmogorov-Smirnov statistical testing. RESULTS: The radiographic density (mean+/-standard deviation in Hounsfield units) of cysts was greater on 100-kVp than on 120-kVp CT scans for both 5-mm and 2-mm reconstructed slice thicknesses: 16.6+/-5.6 versus 10.9+/-4.9 and 14.1+/-5.6 versus 8.5+/-3.9, respectively. CONCLUSIONS: Decrease in tube voltage significantly increases measured radiographic density of renal cysts on CT. Further studies are indicated to assess the clinical impact of lower-tube-voltage CT.

Improved performance of SPECT-CT In-111 capromab pendetide by correlation with diffusion-weighted magnetic resonance imaging for identifying metastatic pelvic lymphadenopathy in prostate cancer.

PURPOSE: To preliminarily evaluate the potential for an improvement in diagnostic performance by a combined interpretation of In-111 capromab pendetide single photon emission computed tomography (SPECT) including computed tomography (CT) image fusion with magnetic resonance diffusion-weighted imaging (MR-DWI) for identifying prostate cancer in pelvic lymph nodes thru correlation with histopathology. MATERIALS AND METHODS: This institutional approved, retrospective study identified patients with available histopathology of lymph nodes removed at the time of radical prostatectomy and who had undergone staging with In-111 capromab pendetide SPECT-CT and/or pelvic MRI (including DWI). The performance of In-111 capromab pendetide SPECT for identifying malignant lymph nodes was assessed. Subsequently, a combined reading of In-111 capromab pendetide SPECT and prostate MRI with DWI was performed and the performance assessed. RESULTS: 18 patients underwent In-111 capromab pendetide SPECT-CT. Of these, 12 patients had also undergone imaging with MR-DWI. In-111 capromab pendetide SPECT-CT had a sensitivity of 40.0% and specificity of 96.7% for identification of malignant lymph nodes. However, In-111 capromab pendetide SPECT-CT combined with MRI with DWI had a sensitivity of 88.9% and specificity of 98.5%. CONCLUSIONS: The addition of MR-DWI to the interpretation of In-111 capromab pendetide SPECT-CT may increase the sensitivity for detecting malignant lymph nodes in prostate cancer. Future prospective evaluation of combined In-111 capromab pendetide SPECT-CT and MR-DWI is indicated and may improve clinical evaluation of nodal disease in prostate cancer.

Simulation study of a quasi-monochromatic beam for x-ray computed mammotomography.

The purpose of this simulation study was to evaluate the feasibility, benefits, and potential operating parameters of a quasi-monochromatic beam from a tungsten-target x-ray source yielding projection images. The application is intended for newly developed cone beam computed mammotomography (CmT) of an uncompressed breast. The value of a near monochromatic x-ray source for a fully 3D CmT application is the expected improved ability to separate tissues with very small differences in attenuation coefficients. The quasi-monochromatic beam is expected to yield enhanced tomographic image quality along with a low dose, equal to or less than that of dual view x-ray mammography. X-ray spectra were generated with a validated projection x-ray simulation tool (XSpect) for a range of tungsten tube potentials (40-100 kVp), filter materials (Z=51-65), and filter thicknesses (10th to 1000th value layer determined at 60 kVp). The breast was modeled from ICRU-44 breast tissue specifications, and a breast lesion was modeled as a 0.5 cm thick mass. The detector was modeled as a digital flat-panel detector with a 0.06 cm thick CsI x-ray absorption layer. Computed figures of merit (FOMs) included the ratio of mean beam energy post-breast to pre-breast and the ratio of lesion contrasts for edge-located and center-located lesions as indices of breast beam hardening, and SNR2/exposure and SNR2/dose as indices of exposure and dose efficiencies. The impact of optimization of these FOMs on lesion contrast is also examined. For all simulated filter materials at each given attenuation thickness [10th, 100th, 500th, 1000th value layers (VLs)], the mean and standard deviation of the pre-breast spectral full-width at tenth-maximum (FWTM) were 16.1 +/- 2.4, 10.3 +/- 2.2, 7.3 +/- 1.4, and 6.5 +/- 1.5 keV, respectively. The change in beam width at the tenth maximum from pre-breast to post-breast spectra ranged from 4.7 to 1.1 keV, for the thinnest and thickest filters, respectively. The higher Z filters (Z=57-63) produced a quasi-monochromatic beam that allowed the widest tube potential operating range (50-70 kVp) while maintaining minimal beam hardening and maximal SNR2/exposure and SNR2/dose, and providing a contrast greater than that obtained in the unfiltered case. Figures of merit improved with increasing filter thickness, with diminishing returns beyond the 500th value layer attenuation level. Operating parameters required to produce optimal spectra, while keeping exposures equal to that of dual view mammography, are within the capability of the commercial x-ray tube proposed for our experimental study, indicating that use of these highly attenuating filters is viable. Additional simulations comparing Mo/Mo, Mo/Rh, and W/Rh target/filter combinations indicate that they exhibit significantly lower SNR2/exposure than the present approach, precluding them from being used for computed mammotomography, while maintaining dose limitations and obtaining sufficient SNR. Beam hardening was also much higher in the existing techniques (17%-42%) than for our technique (2%). Simulations demonstrate that this quasi-monochromatic x-ray technique may enhance tissue separation for a newly developed cone beam computed mammotomography application for an uncompressed breast.