Faculty Bibliography

CONTEXT:Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. OBJECTIVE:To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. EVIDENCE ACQUISITION:An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. EVIDENCE SYNTHESIS:The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. CONCLUSIONS:Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. PATIENT SUMMARY:METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer.

The original version of this article unfortunately contained mistakes. The figures 7D, 7E and 7F were missing in the article and arrows were missing in the figures 6C, 8B and 11C. The year of publication and volume number for references 19, 79 and 87 have been updated. Also, the Table 2 layout has been improved for better readability. The Publisher apologizes for the mistakes and the inconvenience caused.

PURPOSE/OBJECTIVE:To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC). METHODS:IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model. Pairwise inter-site similarities were computed, generating an inter-site similarity matrix (ISM). Inter-site texture heterogeneity metrics were computed from the ISM and compared to clinical outcomes. RESULTS:Of the 12 inter-site texture heterogeneity metrics evaluated, those capturing the differences in texture similarities across sites were associated with shorter overall survival (inter-site similarity entropy, similarity level cluster shade, and inter-site similarity level cluster prominence; p ≤ 0.05) and incomplete surgical resection (similarity level cluster shade, inter-site similarity level cluster prominence and inter-site cluster variance; p ≤ 0.05). Neither the total number of disease sites per patient nor the overall tumour volume per patient was associated with overall survival. Amplification of 19q12 involving cyclin E1 gene (CCNE1) predominantly occurred in patients with more heterogeneous inter-site textures. CONCLUSION/CONCLUSIONS:Quantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC. KEY POINTS/CONCLUSIONS:• Calculating inter-site texture-based heterogeneity metrics was feasible • Metrics capturing texture similarities across HGSOC sites were associated with overall survival • Heterogeneity metrics were also associated with incomplete surgical resection of HGSOC.

PURPOSE:Bone lesions on prostate MRI often raise concern about metastases. This study aimed to evaluate the prevalence of bone metastases on staging prostate MRI and evaluate associations between their MRI features and clinical/pathologic characteristics. METHODS:Retrospective, IRB-approved study of 3765 patients undergoing prostate MRI for newly diagnosed PCa between 2000 and 2014. The reference standard to calculate the prevalence of bone metastases was bone biopsy and/or ≥1-year follow-up after MRI. In a subsample of 228 patients, the MRI characteristics of bone lesions were recorded by two radiologists independently. Associations between MRI and clinical/pathologic findings, including National Comprehensive Cancer Network (NCCN) risk categories, were calculated. RESULTS:57/3765 patients (1.5%, 95% CI 1.2-2.0%) had bone metastases. No patient with NCCN low-risk PCa (Gleason < 7, PSA < 10 ng/mL, cT1-2a) had bone metastases. In the subsample, ≥1 bone lesion was present on MRI in 74% (95% CI 0.67-0.79) and 72% (95% CI 0.66-0.78) of patients (R1 and R2). Larger lesion diameter (OR 1.33/1.19; p < 0.001 for both readers) and the absence of intralesional fat (OR 0.07/0.11; p = 0.004/0.002 for R1/R2) were significantly associated with bone metastases. CONCLUSION:Bone lesions are common in prostate MRI, but only rarely represent metastases. MRI should be interpreted in the context of clinical features that influence the likelihood of metastatic disease.

BACKGROUND:Clinical trials evaluating the benefit of pelvic radiotherapy (PRT) in the radiotherapeutic management of patients with higher-risk prostate cancer have limited the superior field border to the S1/S2 or L5/S1 interspace. However, imaging and surgical series have demonstrated a high frequency of prostatic lymph node (LN) drainage beyond these landmarks. OBJECTIVE:To determine the patterns of radiographically defined abdominopelvic LN failures and their potential implications for PRT field design. DESIGN, SETTING, AND PARTICIPANTS:During 1992-2008, 2694 patients with localized prostate cancer were treated with prostate/seminal vesicle-only radiotherapy without PRT. Some 156 patients had their first failure within the abdominopelvic LNs, of whom 60 had isolated failures within the pelvic LNs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:A radiologist reviewed all imaging and mapped each LN failure to a template consisting of 34 abdominopelvic LN stations. RESULTS AND LIMITATIONS:The median follow-up was 8.9 yr. Of patients who experienced first recurrence in the pelvic LNs (n=60), the common iliac station was involved in 55% (n=33) of patients, including 10% (n=6) who had isolated common iliac failures. Use of a PRT field superior border of L5/S1 would fully cover only 42% of the first recurrences among these patients. Extending the field to cover the common iliac stations would increase coverage to 93% of recurrences. The presence of T3/T4 disease and omission of androgen-deprivation therapy both independently conferred an approximate fivefold increase in the likelihood of having a common iliac LN failure. Use of imaging as a surrogate for LN involvement is the primary study limitation. CONCLUSIONS:Pelvic LN failures frequently occur superior to the commonly used L5/S1 landmark for PRT coverage, and use of ADT may be protective of more superior LN failures. The current RTOG 0924 trial is evaluating the benefit of PRT with extended superior coverage to L4/5 when possible, which, according to our data, should significantly improve the coverage of potential sites of failure. PATIENT SUMMARY:We looked at lymph node recurrence patterns after external beam radiotherapy of the prostate in men who did not have their lymph nodes treated. We found that there was a high incidence of pelvic lymph node recurrences above the internal and external iliac lymph node regions. Therefore, the current field recommendation for pelvic lymph nodes that stops at the superior border of the internal and external iliac vessels provides inadequate coverage of common sites of cancer recurrence, namely the common iliac lymph nodes.

Tumour heterogeneity in cancers has been observed at the histological and genetic levels, and increased levels of intra-tumour genetic heterogeneity have been reported to be associated with adverse clinical outcomes. This review provides an overview of radiomics, radiogenomics, and habitat imaging, and examines the use of these newly emergent fields in assessing tumour heterogeneity and its implications. It reviews the potential value of radiomics and radiogenomics in assisting in the diagnosis of cancer disease and determining cancer aggressiveness. This review discusses how radiogenomic analysis can be further used to guide treatment therapy for individual tumours by predicting drug response and potential therapy resistance and examines its role in developing radiomics as biomarkers of oncological outcomes. Lastly, it provides an overview of the obstacles in these emergent fields today including reproducibility, need for validation, imaging analysis standardisation, data sharing and clinical translatability and offers potential solutions to these challenges towards the realisation of precision oncology.

OBJECTIVE:To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with non-castrate metastatic prostate cancers that are incurable with single modality therapy. MATERIALS AND METHODS:Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary end point was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. RESULTS:Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval: 3%-38%) achieved the primary end point, which persisted for 5, 6, 27+ , and 46+ months. All patients meeting the primary end point had been classified with M1b disease at presentation. CONCLUSION:A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The end point of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and to shift the paradigm from palliation to cure.

PURPOSE/OBJECTIVE:To investigate whether qualitative magnetic resonance (MR) features can distinguish leiomyosarcoma (LMS) from atypical leiomyoma (ALM) and assess the feasibility of texture analysis (TA). METHODS:This retrospective study included 41 women (ALM = 22, LMS = 19) imaged with MRI prior to surgery. Two readers (R1, R2) evaluated each lesion for qualitative MR features. Associations between MR features and LMS were evaluated with Fisher's exact test. Accuracy measures were calculated for the four most significant features. TA was performed for 24 patients (ALM = 14, LMS = 10) with uniform imaging following lesion segmentation on axial T2-weighted images. Texture features were pre-selected using Wilcoxon signed-rank test with Bonferroni correction and analyzed with unsupervised clustering to separate LMS from ALM. RESULTS:Four qualitative MR features most strongly associated with LMS were nodular borders, haemorrhage, "T2 dark" area(s), and central unenhanced area(s) (p ≤ 0.0001 each feature/reader). The highest sensitivity [1.00 (95%CI:0.82-1.00)/0.95 (95%CI: 0.74-1.00)] and specificity [0.95 (95%CI:0.77-1.00)/1.00 (95%CI:0.85-1.00)] were achieved for R1/R2, respectively, when a lesion had ≥3 of these four features. Sixteen texture features differed significantly between LMS and ALM (p-values: <0.001-0.036). Unsupervised clustering achieved accuracy of 0.75 (sensitivity: 0.70; specificity: 0.79). CONCLUSIONS:Combination of ≥3 qualitative MR features accurately distinguished LMS from ALM. TA was feasible. KEY POINTS/CONCLUSIONS:• Four qualitative MR features demonstrated the strongest statistical association with LMS. • Combination of ≥3 these features could accurately differentiate LMS from ALM. • Texture analysis was a feasible semi-automated approach for lesion categorization.