To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer.
Between June ...2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy CIMRT) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT HIMRT); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed.
There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT.
The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.
•MRI simulation was utilized to measure texture dependence on MR acquisition details.•Texture was measured on a digital brain phantom and clinical brain images.•Texture depends on noise, ...reconstruction algorithm, and parallel imaging R-factor.•Some texture features can be very different from the ground truth values.•Texture features are more or less robust and some predict high vs low grade glioma.
The purpose of this study was to examine the dependence of image texture features on MR acquisition parameters and reconstruction using a digital MR imaging phantom. MR signal was simulated in a parallel imaging radiofrequency coil setting as well as a single element volume coil setting, with varying levels of acquisition noise, three acceleration factors, and four image reconstruction algorithms. Twenty-six texture features were measured on the simulated images, ground truth images, and clinical brain images. Subtle algorithm-dependent errors were observed on reconstructed phantom images, even in the absence of added noise. Sources of image error include Gibbs ringing at image edge gradients (tissue interfaces) and well-known artifacts due to high acceleration; two of the iterative reconstruction algorithms studied were able to mitigate these image errors. The difference of the texture features from ground truth, and their variance over reconstruction algorithm and parallel imaging acceleration factor, were compared to the clinical “effect size”, i.e., the feature difference between high- and low-grade tumors on T1- and T2-weighted brain MR images of twenty glioma patients. The measured feature error (difference from ground truth) was small for some features, but substantial for others. The feature variance due to reconstruction algorithm and acceleration factor were generally smaller than the clinical effect size. Certain texture features may be preserved by MR imaging, but adequate precautions need to be taken regarding their validity and reliability. We present a general simulation framework for assessing the robustness and accuracy of radiomic textural features under various MR acquisition/reconstruction scenarios.
Abstract Background Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). Objective To evaluate the ability of ...biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). Design, setting, and participants Two hundred and thirty-five patients treated with either RP ( n = 105) or RT ± androgen deprivation therapy ( n = 130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model. Outcome measurements and statistical analysis Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher. Results and limitations With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval CI: 1.06–1.78, p = 0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50–0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60–0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53–0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66–0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03–2.48, p = 0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively. Conclusions Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP. Patient summary Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens.
To evaluate the performance of mpMRI and the 4Kscore test together for the detection of significant prostate cancer. Material and methods We selected a consecutive series of men who were referred for ...evaluation of prostate cancer at an academic institution and underwent mpMRI and the 4Kscore test. The primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the prostate. We used logistic regression and Decision Curve Analysis to report the discrimination and clinical utility of using mpMRI and the 4Kscore test for prostate cancer detection. We modeled the probability of harboring a Gleason 7 or higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we examined various combinations and sequences of mpMRI and the 4Kscore test and assessed the impact on biopsies avoided and cancers missed.
Among 300 men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75-0.89) was superior to using the 4Kscore 0.70 (0.62-0.79) or mpMRI 0.74 (0.66-0.81) individually (p = 0.001). Similarly, decision analysis revealed the highest net benefit was achieved using both tests.
The 4Kscore test and mpMRI results provide independent, but complementary, information that enhances the prediction of higher-grade prostate cancer and improves patient's selection for a prostate biopsy. Prospective trials are required to confirm these findings.
For prostate cancer (PCa) patients treated with definitive radiotherapy (RT), acute and late RT-related genitourinary (GU) toxicities adversely impact disease-specific quality of life. Early warning ...of potential RT toxicities can prompt interventions that may prevent or mitigate future adverse events. During intensity modulated RT (IMRT) of PCa, daily cone-beam computed tomography (CBCT) images are used to improve treatment accuracy through image guidance. This work investigated the performance of CBCT-based delta-radiomic features (DRF) models to predict acute and sub-acute International Prostate Symptom Scores (IPSS) and Common Terminology Criteria for Adverse Events (CTCAE) version 5 GU toxicity grades for 50 PCa patients treated with definitive RT. Delta-radiomics models were built using logistic regression, random forest for feature selection, and a 1000 iteration bootstrapping leave one analysis for cross validation. To our knowledge, no prior studies of PCa have used DRF models based on daily CBCT images. AUC of 0.83 for IPSS and greater than 0.7 for CTCAE grades were achieved as early as week 1 of treatment. DRF extracted from CBCT images showed promise for the development of models predictive of RT outcomes. Future studies will include using artificial intelligence and machine learning to expand CBCT sample sizes available for radiomics analysis.
To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying ...information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient. In radiation therapy of GBM the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl aspartate (NAA) and choline (Cho). The corresponding clinical target volumes (CTVs) for radiation therapy are based on contrast-enhanced T1-weighted (CE-T1w) and T2-weighted (T2w)/fluid-attenuated inversion recovery MRI.
Necrotic portions, enhancing lesion, and edema were manually contoured on CE-T1w/T2w images for 17 GBM patients. Clinical target volumes and MTVs for NAA (MTV
) and Cho (MTV
) were constructed. Imaging and metabolic features related to size, shape, and signal intensities of the volumes were extracted. Tumors were also scored categorically for 10 semantic imaging traits by a neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and CTVs/MTVs features were visualized as heatmaps. Associations between MTV
and MTV
and imaging features were studied using Spearman correlation.
Forty-eight imaging features were extracted per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. Twenty features were extracted from CTVs and MTVs. A series of semantic imaging traits were replaced with automatically extracted continuous variables. There were multiple (22) significant correlations of imaging measures with CTVs/MTV
, whereas there were only 6 with CTVs/MTV
.
A framework for investigation of codependencies between MRI and magnetic resonance spectroscopic imaging radiomic features and CTVs/MTVs has been established. The MTV for NAA was found to be closely associated with MRI volumes, whereas very few imaging features were related to MTV
, indicating that Cho provides additional information to imaging.
MRI is the standard modality to assess anatomy and response to treatment in brain and spine tumors given its superb anatomic soft tissue contrast (e.g., T1 and T2) and numerous additional intrinsic ...contrast mechanisms that can be used to investigate physiology (e.g., diffusion, perfusion, spectroscopy). As such, hybrid MRI and radiotherapy (RT) devices hold unique promise for Magnetic Resonance guided Radiation Therapy (MRgRT). In the brain, MRgRT provides daily visualizations of evolving tumors that are not seen with cone beam CT guidance and cannot be fully characterized with occasional standalone MRI scans. Significant evolving anatomic changes during radiotherapy can be observed in patients with glioblastoma during the 6-week fractionated MRIgRT course. In this review, a case of rapidly changing symptomatic tumor is demonstrated for possible therapy adaptation. For stereotactic body RT of the spine, MRgRT acquires clear isotropic images of tumor in relation to spinal cord, cerebral spinal fluid, and nearby moving organs at risk such as bowel. This visualization allows for setup reassurance and the possibility of adaptive radiotherapy based on anatomy in difficult cases. A review of the literature for MR relaxometry, diffusion, perfusion, and spectroscopy during RT is also presented. These techniques are known to correlate with physiologic changes in the tumor such as cellularity, necrosis, and metabolism, and serve as early biomarkers of chemotherapy and RT response correlating with patient survival. While physiologic tumor investigations during RT have been limited by the feasibility and cost of obtaining frequent standalone MRIs, MRIgRT systems have enabled daily and widespread physiologic measurements. We demonstrate an example case of a poorly responding tumor on the 0.35 T MRIgRT system with relaxometry and diffusion measured several times per week. Future studies must elucidate which changes in MR-based physiologic metrics and at which timepoints best predict patient outcomes. This will lead to early treatment intensification for tumors identified to have the worst physiologic responses during RT in efforts to improve glioblastoma survival.
Objective
Denosumab is an established targeted systemic therapy for treatment of giant cell tumor of bone (GCTB). We sought to determine whether treatment response could be quantified from radiomics ...analysis of radiographs taken longitudinally during treatment.
Materials and methods
Pre- and post-treatment radiographs of 10 GCTB tumors from 10 patients demonstrating histologic response after treatment with denosumab were analyzed. Intensity- and texture-based radiomics features for each manually segmented tumor were calculated. Radiomics features were compared pre- and post-treatment in tumors.
Results
Mean intensity (
p
= 0.033) significantly increased while skewness (
p
= 0.028) significantly decreased after treatment. Post-treatment increases in fractal dimensions (
p
= 0.057) and abundance (
p
= 0.065) approached significance. A potential linear correlation in mean (
p
= 0.005; ΔMean = 0.022 * duration − 0.026) with treatment duration was observed.
Conclusion
Radiomics analysis of plain radiographs quantifies time-dependent matrix mineralization and trabecular reconstitution that mark positive response of giant cell tumors of bone to denosumab.
Background. Historically, intraductal carcinoma of the prostate (IDC-P) was postulated to be a retrograde spread of high-grade invasive prostate cancer. There is evidence that IDC-P can primarily ...originate in the prostatic ducts. The retrograde genesis has never been experimentally or clinically confirmed before. Methods. Biopsy proven intermediate or high-risk prostate cancer was orthotopically grafted in the prostate of severe combined immunodeficiency gamma mice. Cancer growth was monitored by serum PSA levels. The animals were sacrificed and grafted areas were histological examined. Results. Twenty-one of 23 mice survived and demonstrated rising serum PSA. In 10 of 21 animals, human prostate cancer was identified orthotopically. Except for one case where the human biopsy showed a Grade Group 2 prostate cancer and mouse graft was Grade Group 5, other 9 specimens showed comparable grades. One of the specimens demonstrated a cribriform invasive prostate cancer and adjacent IDC-P. Conclusion. These experimental data offer some evidence that invasive prostate cancer can demonstrate a retrograde spread in the prostatic ducts as IDC-P. Its ability to primarily arise in the ducts has been demonstrated in other studies. However, the issue which remains unresolved is in its most common presentation of IDC-P intermixed with high-grade invasive cancer if it is the former or the latter which came first. Possibly resolving this dilemma will shed some light on the existing controversies if IDC-P should or should not be graded when invasive cancer is present.
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