Gregory Cooley, MD

Prostate specific membrane antigen (PSMA)-based radiotracers have shown promise for prostate cancer assessment. Evaluation of quantitative variability and establishment of reference standards are important for optimal clinical and research utility. This work evaluates the variability of PSMA-based [18F]DCFPyL (PyL) PET quantitative reference standards. Consecutive eligible patients with biochemically recurrent prostate cancer were recruited for study participation from August 2016-October 2017. After PyL tracer injection, whole body PET/CT (wbPET/CT) was obtained with subsequent whole body PET/MR (wbPET/MR). Two readers independently created regions of interest (ROIs) including a 40% standardized uptake value (SUV) threshold ROI of the whole right parotid gland and separate spherical ROIs in the superior, mid, and inferior gland. Additional liver (right lobe) and blood pool spherical ROIs were defined. Bland-Altman analysis, including limits of agreement (LOA), as well as interquartile range (IQR) and coefficient of variance (CoV) was used. Twelve patients with prostate cancer were recruited (mean age, 61.8 yrs; range 54-72 years). One patient did not have wbPET/MR and was excluded. There was minimal inter-reader SUVmean variability (bias±LOA) for blood pool (-0.13±0.42; 0.01±0.41), liver (-0.55±0.82; -0.22±1.3), or whole parotid gland (-0.05±0.31; 0.08±0.24) for wbPET/CT and wbPET/MR, respectively. Greater inter-reader variability for the 1-cm parotid gland ROIs was present, for both wbPET/CT and wbPET/MR. Comparing wbPET/CT to the subsequently acquired wbPET/MR, blood pool had a slight decrease in SUVmean. The liver as well as parotid gland showed a slight increase in activity although the absolute bias only ranged from 0.45-1.28. The magnitude of inter-subject variability was higher for the parotid gland regardless of modality or reader. In conclusion, liver, blood pool, and whole parotid gland quantitation show promise as reliable reference normal organs for clinical/research PET applications. Variability with 1-cm parotid ROIs may limit its use.

PMID:37023049 | PMC:PMC10079029 | DOI:10.1371/journal.pone.0283830

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

PMID:34024743 | DOI:10.1016/j.clgc.2021.04.010

PURPOSE: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging.

EXPERIMENTAL DESIGN: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety.

RESULTS: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8-80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers).

CONCLUSIONS: Performance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.See related commentary by True and Chen, p. 3512.

PMID:33622706 | PMC:PMC8382991 | DOI:10.1158/1078-0432.CCR-20-4573

The objective of this work is to evaluate biological models and dose homogeneity in a new partial breast irradiation method, the MammoSite RTS. The study is based on 11 patients who received the therapy. For each patient, we determined the dose volume distribution delivered to the breast. Based on these data, we estimate some important biological parameters. Eleven patients with early-stage, invasive, ductal breast cancer were treated using MammoSite RTS brachytherapy, which delivers radiation through a balloon placed in the lumpectomy bed. The radiation was provided by an Iridium-192 source, and 340 cGy were delivered per fraction twice daily. We calculated some commonly used dosimetric parameters, and evaluated the biological parameters tumor control probability (TCP) and normal tissue complication probability (NTCP). We also looked for correlations among these parameters. The average equivalent uniform dose (EUD), NTCP, and TCP were 43.66 Gy, 47.95%, and 91.78%, respectively. The coefficient of variation (CV) among the patients was very low for all 3 parameters. Two dose homogeneity indices (DHI and the S-index) are strongly correlated (r = -0.815). The area under the dose-volume histogram (DVH) and the treatment volume (TXV) also showed a strong correlation (r = 0.995, p < 0.0001). A simplified logit Poisson-EUD model is suitable for determining NTCP and TCP. Other factors such as the area under the DVH and dose homogeneity indices are also useful in planning radiotherapy treatments for early breast cancer.

PMID:19647630 | DOI:10.1016/j.meddos.2008.08.003

This study assesses the agreement between computed tomography (CT) measurements of prostate volume and those obtained by ultrasound (US), a well-established non-invasive technique. Twenty-six patients aged between 58 and 74 years were evaluated for prostate seed implant therapy using both CT and US measurements. The level of agreement between these 2 methods, which were strongly correlated (R2 = 0.828; p < 0.0001), was determined through Bland-Altman analysis. The mean prostate volume (+/- one standard deviation) of the sample was 31.8 +/- 10.5 cc for the CT method and 27.0 +/- 8.2 cc for the US method. The prostate volumes obtained by CT were, on average, 17% larger than the corresponding volumes determined by US. The average bias between the 2 imaging methods is 4.80 cc or 15%, which is significantly larger than the clinically acceptable margin of 10%.

PMID:18674689 | DOI:10.1016/j.meddos.2008.01.001