•High interobserver variability (IoV) was observed at junctions between the prostate and one or more organs at risk.•Radiation oncologists were the most consistent group of observers, but high IoV ...was still observed in this group.•IoV demonstrated a dependence on organ size, and was highest for the external urinary sphincter.•High IoV was observed on both treatment planning MRIs and postimplant quality assessment MRIs.•Dose-volume-histogram parameters for MRI-based prostate radiotherapy are heavily influenced by IoV.
Quantifying the interobserver variability (IoV) of prostate and periprostatic anatomy delineation on prostate MRI is necessary to inform its use for treatment planning, treatment delivery, and treatment quality assessment.
Twenty five prostate cancer patients underwent MRI-based low-dose-rate prostate brachytherapy (LDRPBT). The patients were scanned with a 3D T2-weighted sequence for treatment planning and a 3D T2/T1-weighted sequence for quality assessment. Seven observers involved with the LDRPBT workflow delineated the prostate, external urinary sphincter (EUS), seminal vesicles, rectum, and bladder on all 50 MRIs. IoV was assessed by measuring contour similarity metrics, differences in organ volumes, and differences in dosimetry parameters between unique observer pairs. Measurements from a group of 3 radiation oncologists (G1) were compared against those from a group consisting of the other 4 clinical observers (G2).
IoV of the prostate was lower for G1 than G2 (Matthew’s correlation coefficient MCC, G1 vs. G2: planning–0.906 vs. 0.870, p < 0.001; postimplant–0.899 vs. 0.861, p < 0.001). IoV of the EUS was highest of all the organs for both groups, but was lower for G1 (MCC, G1 vs. G2: planning–0.659 vs. 0.402, p < 0.001; postimplant–0.684 vs. 0.398, p < 0.001). Large differences in prostate dosimetry parameters were observed (G1 maximum absolute prostate ΔD90: planning–76.223 Gy, postimplant–36.545 Gy; G1 maximum absolute prostate ΔV100: planning–13.927%, postimplant–8.860%).
While MRI is optimal in the management of prostate cancer with radiation therapy, significant interobserver variability of the prostate and external urinary sphincter still exist.
P-glycoprotein (Pgp) antagonists have been difficult to develop because of complex pharmacokinetic interactions and a failure to show meaningful results. Here we report the results of a ...pharmacokinetic and pharmacodynamic trial using a third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576), in combination with docetaxel.
In the first treatment cycle, the pharmacokinetics of docetaxel (40 mg/m(2)) were evaluated after day 1 and day 8 doses, which were administered with or without tariquidar (150 mg). (99m)Tc-sestamibi scanning and CD56(+) mononuclear cell rhodamine efflux assays were conducted to assess Pgp inhibition. In subsequent cycles, 75 mg/m(2) docetaxel was administered with 150 mg tariquidar every 3 weeks.
Forty-eight patients were enrolled onto the trial. Nonhematologic grade 3/4 toxicities in 235 cycles were minimal. Tariquidar inhibited Pgp-mediated rhodamine efflux from CD56(+) cells and reduced (99m)Tc-sestamibi clearance from the liver. There was striking variability in basal sestamibi uptake; a 12% to 24% increase in visible lesions was noted in 8 of 10 patients with lung cancer. No significant difference in docetaxel disposition was observed in pairwise comparison with and without tariquidar. Four partial responses (PR) were seen (4/48); 3 in the non-small cell lung cancer (NSCLC) cohort, measuring 40%, 57%, and 67% by RECIST, and 1 PR in a patient with ovarian cancer.
Tariquidar is well tolerated, with less observed systemic pharmacokinetic interaction than previous Pgp antagonists. Variable effects of tariquidar on retention of sestamibi in imageable lung cancers suggest that follow-up studies assessing tumor drug uptake in this patient population would be worthwhile.
To describe clinical use and potential benefits of cone-beam computed tomography (CT) navigation to perform image-guided percutaneous tumor ablation.
All ablations performed between February 2011 and ...February 2013 using cone-beam CT navigation were included. There were 16 patients who underwent 20 ablations for 29 lesions. Cone-beam CT ablation planning capabilities include multimodality image fusion and tumor segmentation for visualization, depiction of the predicted ablation zones for intraprocedural planning, and segmentation of the ablated area for immediate verification after treatment. Number and purpose of cone-beam CT scans were examined. The initial ablation plan, defined as number of probes and duration of energy delivery, was recorded for the 20 of the 29 lesions ablated. Technical success and local recurrences were recorded. Primary and secondary effectiveness rates were calculated.
Image fusion was used for 16 lesions, and intraprocedural ultrasound was used for 4 lesions. Of the 20 ablations, where the ablation plans were recorded, there was no deviation from the plan in 14 ablations. In the remaining 6 ablations, iterative planning was needed for complete tumor coverage. An average of 8.7 cone-beam CT scans ± 3.2 were performed per procedure, including 1.3 ± 0.5 for tumor segmentation and planning, 1.7 ± 0.7 for probe position confirmation, and 3.9 ± 2 to ensure complete coverage. Mean follow-up time was 18.6 months ± 6.5. Ablations for 28 of 29 lesions were technically successful (96.5%). Of ablations performed with curative intent, technical effectiveness at 1 month was 25 of 26 lesions (96.1%) and 22 of 26 lesions (84.6%) at last follow-up. Local tumor progression was observed in 11.5% (3 of 26 lesions).
Cone-beam CT navigation may add information to assist and improve ablation guidance and monitoring.
To investigate fully balanced steady-state free precession (bSSFP) with optimized acquisition protocols for magnetic resonance imaging (MRI)-based postimplant quality assessment of low-dose-rate ...(LDR) prostate brachytherapy without an endorectal coil (ERC).
Seventeen patients at a major academic cancer center who underwent MRI-assisted radiosurgery (MARS) LDR prostate cancer brachytherapy were imaged with moderate, high, or very high spatial resolution fully bSSFP MRIs without using an ERC. Between 1 and 3 signal averages (NEX) were acquired with acceleration factors (R) between 1 and 2, with the goal of keeping scan times between 4 and 6 minutes. Acquisitions with R >1 were reconstructed with parallel imaging and compressed sensing (PICS) algorithms. Radioactive seeds were identified by 3 medical dosimetrists. Additionally, some of the MRI techniques were implemented and tested at a community hospital; 3 patients underwent MARS LDR prostate brachytherapy and were imaged without an ERC.
Increasing the in-plane spatial resolution mitigated partial volume artifacts and improved overall seed and seed marker visualization at the expense of reduced signal-to-noise ratio (SNR). The reduced SNR as a result of imaging at higher spatial resolution and without an ERC was partially compensated for by the multi-NEX acquisitions enabled by PICS. Resultant image quality was superior to the current clinical standard. All 3 dosimetrists achieved near-perfect precision and recall for seed identification in the 17 patients. The 3 postimplant MRIs acquired at the community hospital were sufficient to identify 208 out of 211 seeds implanted without reference to computed tomography (CT).
Acquiring postimplant prostate brachytherapy MRI without an ERC has several advantages including better patient tolerance, lower costs, higher clinical throughput, and widespread access to precision LDR prostate brachytherapy. This prospective study confirms that the use of an ERC can be circumvented with fully bSSFP and advanced MRI scan techniques in a major academic cancer center and community hospital, potentially enabling postimplant assessment of MARS LDR prostate brachytherapy without CT.
•Different loss functions for developing deep learning (DL) algorithms can change prostate and organs at risk (OAR) boundaries, particularly in anatomical regions with high interobserver ...variability.•DL-based automatic segmentation algorithms exhibit high variability in similar anatomical regions as the humans who annotated the images for the DL algorithm development.•Spatial entropy maps provide an intuitive characterization of voxel-wise segmentation variability.•DL-based automatic segmentation algorithms can be more consistent than human observers in delineating the prostate and OARs on MRIs for prostate radiotherapy.•Segmentation performance of T2-weighted planning MRIs was comparable to that of T2/T1-weighted postimplant MRIs.
Comparing deep learning (DL) algorithms to human interobserver variability, one of the largest sources of noise in human-performed annotations, is necessary to inform the clinical application, use, and quality assurance of DL for prostate radiotherapy.
One hundred fourteen DL algorithms were developed on 295 prostate MRIs to segment the prostate, external urinary sphincter (EUS), seminal vesicles (SV), rectum, and bladder. Fifty prostate MRIs of 25 patients undergoing MRI-based low-dose-rate prostate brachytherapy were acquired as an independent test set. Groups of DL algorithms were created based on the loss functions used to train them, and the spatial entropy (SE) of their predictions on the 50 test MRIs was computed. Five human observers contoured the 50 test MRIs, and SE maps of their contours were compared with those of the groups of the DL algorithms. Additionally, similarity metrics were computed between DL algorithm predictions and consensus annotations of the 5 human observers’ contours of the 50 test MRIs.
A DL algorithm yielded statistically significantly higher similarity metrics for the prostate than did the human observers (H) (prostate Matthew’s correlation coefficient, DL vs. H: planning–0.931 vs. 0.903, p < 0.001; postimplant–0.925 vs. 0.892, p < 0.001); the same was true for the 4 organs at risk. The SE maps revealed that the DL algorithms and human annotators were most variable in similar anatomical regions: the prostate-EUS, prostate-SV, prostate-rectum, and prostate-bladder junctions.
Annotation quality is an important consideration when developing, evaluating, and using DL algorithms clinically.
Background The aim of this study was to prospectively screen patients with a positive family history of carcinoid small intestine neuroendocrine tumors (SI-NETs) to elucidate the benefits of early ...detection and operative intervention. Methods A single-center, prospective trial was conducted from 2008 to 2014 that evaluated patients with 2 or more blood relatives with carcinoid SI-NETs. All eligible patients were screened with urine/serum biochemistries and various imaging modalities. Operative intervention was elected in patients found to have at least 1 positive diagnostic study. Results Twenty-nine patients from 13 families had occult carcinoid SI-NETs (15 female, 14 male). Twenty-four of the 29 patients (83%) had multifocal disease found in either the distal jejunum or ileum. On average, 75.9 cm (range, 13–195) of bowel was resected in 1 segment. Three patients were found to have stage IV disease at operation. All stage I-IIIB patients who had R0 resections have remained disease-free, with a median follow-up of 35 months. Conclusion Familial carcinoid SI-NETs often are asymptomatic and can be diagnosed with aggressive screening. With early detection, there may be a window of opportunity for operative resection to change the natural history of this disease and even prove to be curative.
Background
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency which can lead to gastrointestinal (GI) complications including inflammatory bowel disease. Radiographic findings in ...this cohort have not been well described.
Aims
To describe the frequency and spectrum of gastrointestinal abnormalities seen on computed tomography (CT) in patients with CGD and determine whether radiography was predictive of endoscopic or histopathologic inflammatory findings.
Methods
A retrospective review was conducted on 141 consecutive CGD patients seen at the National Institutes of Health between 1988 and 2011. All corresponding CTs were reviewed for gastrointestinal abnormalities including wall thickening. Endoscopic and histopathologic findings were reviewed in subjects with documented endoscopy within 30 days of an imaging study. Findings were compared between patients with and without wall thickening on CT to determine whether bowel wall thickening was predictive of endoscopic or histologic inflammatory findings.
Results
Two hundred and ninety-two CTs were reviewed. GI wall thickening was present on CT in 61% of patients (
n
= 86). Among a subgroup of 20 patients who underwent endoscopy at the time of their imaging, there was a statistically significant correlation between radiographic gastrointestinal wall thickening and endoscopic inflammation in the same intestinal segment (
p
= 0.035). Additionally, there was a significant correlation between radiographic gastrointestinal wall thickening and inflammatory features on histopathology (
p
= 0.02).
Conclusions
GI abnormalities are commonly observed on CT in CGD patients. Bowel wall thickening correlates with endoscopic and histopathologic evidence of inflammation. These findings may be used to better facilitate directed endoscopic assessment and histopathologic sampling in patients with CGD.
Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and ...clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with
SDHB
-associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring
SDHB
mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750 mg/m
2
cyclophosphamide with 1.4 mg/m
2
vincristine on day 1 and 600 mg/m
2
dacarbazine on days 1 and 2, every 21–28 days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4–41) was administered. All patients had tumor reduction (12–100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478 days, with progression-free and overall survivals of 930 and 1190 days, respectively. Serial
18
F-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUV
max
) values in 26/30 lesions. During treatment administration, the median SUV decreased from > 25 to < 6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic
SDHB
-related PPGL.
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