Focal radiotherapy boost to MR-visible tumor for prostate cancer: a systematic review.

PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.

One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer.

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

A pilot study of MRI radiomics for high-risk prostate cancer stratification in 1.5 T MR-guided radiotherapy.

PURPOSE: To investigate the potential value of MRI radiomics obtained from a 1.5 T MRI-guided linear accelerator (MR-LINAC) for D'Amico high-risk prostate cancer (PC) classification in MR-guided radiotherapy (MRgRT). METHODS: One hundred seventy-six consecutive PC patients underwent 1.5 T MRgRT treatment were retrospectively enrolled. Each patient received one or two pretreatment T2 -weighted MRI scans on a 1.5 T MR-LINAC. The endpoint was to differentiate high-risk from low/intermediate-risk PC based on D'Amico criteria using MRI-radiomics. Totally 1023 features were extracted from clinical target volume (CTV) and planning target volume (PTV). Intraclass correlation coefficient of scan-rescan repeatability, feature correlation, and recursive feature elimination were used for feature dimension reduction. Least absolute shrinkage and selection operator regression was employed for model construction. Receiver operating characteristic area under the curve (AUC) analysis was used for model performance assessment in both training and testing data. RESULTS: One hundred and eleven patients fulfilled all criteria were finally included: 76 for training and 35 for testing. The constructed MRI-radiomics models extracted from CTV and PTV achieved the AUC of 0.812 and 0.867 in the training data, without significant difference (P = 0.083). The model performances remained in the testing. The sensitivity, specificity, and accuracy were 85.71%, 64.29%, and 77.14% for the PTV-based model; and 71.43%, 71.43%, and 71.43% for the CTV-based model. The corresponding AUCs were 0.718 and 0.750 (P = 0.091) for CTV- and PTV-based models. CONCLUSION: MRI-radiomics obtained from a 1.5 T MR-LINAC showed promising results in D'Amico high-risk PC stratification, potentially helpful for the future PC MRgRT. Prospective studies with larger sample sizes and external validation are warranted for further verification.

Convolutional neural network for discriminating nasopharyngeal carcinoma and benign hyperplasia on MRI.

OBJECTIVES: A convolutional neural network (CNN) was adapted to automatically detect early-stage nasopharyngeal carcinoma (NPC) and discriminate it from benign hyperplasia on a non-contrast-enhanced MRI sequence for potential use in NPC screening programs. METHODS: We retrospectively analyzed 412 patients who underwent T2-weighted MRI, 203 of whom had biopsy-proven primary NPC confined to the nasopharynx (stage T1) and 209 had benign hyperplasia without NPC. Thirteen patients were sampled randomly to monitor the training process. We applied the Residual Attention Network architecture, adapted for three-dimensional MR images, and incorporated a slice-attention mechanism, to produce a CNN score of 0-1 for NPC probability. Threefold cross-validation was performed in 399 patients. CNN scores between the NPC and benign hyperplasia groups were compared using Student's t test. Receiver operating characteristic with the area under the curve (AUC) was performed to identify the optimal CNN score threshold. RESULTS: In each fold, significant differences were observed in the CNN scores between the NPC and benign hyperplasia groups (p < .01). The AUCs ranged from 0.95 to 0.97 with no significant differences between the folds (p = .35 to .92). The combined AUC from all three folds (n = 399) was 0.96, with an optimal CNN score threshold of > 0.71, producing a sensitivity, specificity, and accuracy of 92.4%, 90.6%, and 91.5%, respectively, for NPC detection. CONCLUSION: Our CNN method applied to T2-weighted MRI could discriminate between malignant and benign tissues in the nasopharynx, suggesting that it as a promising approach for the automated detection of early-stage NPC. KEY POINTS: • The convolutional neural network (CNN)-based algorithm could automatically discriminate between malignant and benign diseases using T2-weighted fat-suppressed MR images. • The CNN-based algorithm had an accuracy of 91.5% with an area under the receiver operator characteristic curve of 0.96 for discriminating early-stage T1 nasopharyngeal carcinoma from benign hyperplasia. • The CNN-based algorithm had a sensitivity of 92.4% and specificity of 90.6% for detecting early-stage nasopharyngeal carcinoma.

Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

OBJECTIVE: To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APTmean, APT90, APTskewness, and APTkurtosis, respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis. RESULTS: Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APTskewness (HR = 1.98; p = 0.034), DMFS with APTmean (HR = 2.44; p = 0.033), and APT90 (HR = 1.93; p = 0.009), and DFS with APTmean (HR = 2.01; p = 0.016), APT90 (HR = 1.68; p = 0.009), and APTskewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005). CONCLUSION: APTw imaging may potentially predict survival in patients with NPC. KEY POINTS: • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APThigh group is at higher risk of disease relapse than the APTlow group.

Intravoxel incoherent motion diffusion-weighted imaging for discrimination of benign and malignant retropharyngeal nodes.

PURPOSE: Anatomical imaging criteria for the diagnosis of malignant head and neck nodes may not always be reliable. This study aimed to evaluate the diagnostic value of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) DWI in discriminating benign and malignant metastatic retropharyngeal nodes (RPNs). METHODS: IVIM DWI using 14 b-values was performed on RPNs of 30 patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC) and 30 patients with elevated plasma Epstein-Barr virus (EBV)-DNA without NPC who were part of an EBV-based NPC screening program. Histogram measurements of the two groups were compared for pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion volume fraction (f) and apparent diffusion coefficient (ADC) using the Mann-Whitney U test. Area under the curves (AUCs) of significant measurements were calculated from receiver-operating characteristics analysis and compared using the DeLong test. RESULTS: Compared with metastatic RPNs, benign RPNs had lower ADCmean (0.73 vs 0.82 × 10-3 mm2/s) and Dmean (0.60 vs 0.71 × 10-3 mm2/s) and a higher D*mean (35.21 vs 28.66 × 10-3 mm2/s) (all p < 0.05). There was no difference in the f measurements between the two groups (p = 0.204 to 0.301). Dmean achieved the highest AUC of 0.800, but this was not statistically better than the AUCs of the other parameters (p = 0.148 to 0.991). CONCLUSION: Benign RPNs in patients with EBV-DNA showed greater restriction of diffusion compared with malignant metastatic RPNs from NPC. IVIM did not show a significant advantage over conventional DWI in discriminating benign and malignant nodes.

Distinguishing early-stage nasopharyngeal carcinoma from benign hyperplasia using intravoxel incoherent motion diffusion-weighted MRI.

OBJECTIVES: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities. METHODS: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant. RESULTS: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10-3 mm2/s), ADC0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10-3 mm2/s), ADC300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10-3 mm2/s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10-3 mm2/s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10-3 mm2/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia. CONCLUSION: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC300-1000 mean were the most promising parameters. KEY POINTS: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.

Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.

PURPOSE: To determine if treatment of nasopharyngeal carcinoma (NPC) induces early changes in amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI), and to perform a preliminary evaluation of APTw imaging in response assessment. METHODS: Sixteen patients with NPC planned for treatment with radiotherapy and/or chemotherapy underwent APTw imaging of the primary tumour pre-treatment and 2-week intra-treatment. Difference in pre- and intra-treatment APT mean (APTmean) was compared using the Wilcoxon signed rank test. Differences in APTmean and percentage change (%Δ) in APTmean were compared between responders and non-responders based on the outcome at 6 months, using the Mann-Whitney U test. RESULTS: APTmean decreased in 9/16 (56.3%) and increased in 7/16 (43.7%) with no significant difference between the pre- and intra-treatment APT values for the whole group (p > 0.05). NPC showed response in 11/16 (68.8%) and non-response in 5/11 (31.2%). There were significant differences between the %Δ of responders and non-responders for APTmean (p = 0.01). Responders showed %Δ decrease in APTmean of - 23.12% while non-responders showed a %Δ increase in APTmean of + 102.28%. CONCLUSION: APT value changes can be detected in early intra-treatment. Intra-treatment %Δ APTmean shows potential in predicting short-term outcome.

Head and Neck Tumors: Amide Proton Transfer MRI.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in the characterization of head and neck tumors. Materials and Methods This retrospective study of APT imaging included 117 patients with 70 nasopharyngeal undifferentiated carcinomas (NUCs), 26 squamous cell carcinomas (SCCs), eight non-Hodgkin lymphomas (NHLs), and 13 benign salivary gland tumors (BSGTs). Normal tissues were examined in 25 patients. The APT means of malignant tumors, normal tissues, and benign tumors were calculated and compared with the Student t test and analysis of variance. The added value of the mean APT to the mean apparent diffusion coefficient (ADC) for differentiating malignant and benign tumors was evaluated by using receiver operating characteristic analysis and integrated discrimination index. Results The mean APT of malignant tumors (2.40% ± 0.97 [standard deviation]) was significantly higher than that of brain tissue (1.13% ± 0.43), muscle tissue (0.23% ± 0.73), and benign tumors (1.32% ± 1.20) (P < .001). There were no differences between malignant groups (NUC, 2.37% ± 0.90; SCC, 2.41% ± 1.16; NHL, 2.65% ± 0.89; P = .45 to P = .86). The mean ADC of malignant tumors ([0.85 ± 0.17] × 10-3 mm2/sec) was significantly lower than that of benign tumors ([1.46 ± 0.47] × 10-3 mm2/sec) (P = .001). Adding APT to ADC increased the area under the curve from 0.87 to 0.96, with an integrated discrimination index of 7.6% (P = .13). Conclusion These preliminary data demonstrate differences in amide proton transfer (APT) mean of malignant tumors, normal tissues, and benign tumors, although APT mean could not be used to differentiate between malignant tumor groups. APT imaging has the potential to be of added value to apparent diffusion coefficient in differentiating malignant from benign tumors.

Nasopharyngeal carcinoma: relationship between invasion of the prevertebral space and distant metastases.

PURPOSE: To identify primary sites of nasopharyngeal carcinoma (NPC) invasion on the staging head and neck magnetic resonance imaging (MRI) that correlate with distant metastases (DM). MATERIALS AND METHODS: Staging head and neck MRI examinations of 579 NPC patients were assessed for primary tumour invasion into 16 individual sites, primary stage (T) and nodal stage (N). Results were correlated with distant metastasis-free survival (DMFS) using the Cox regression, and the diagnostic performance of significant independent markers for DM was calculated. In addition, sites of primary tumour invasion were correlated also with involvement of the first echelon of ipsilateral nodes (FEN+) using logistic regression. RESULTS: Distant metastases were present in 128/579 NPC patients (22.1%) after intensity-modulated radiotherapy (IMRT)/chemo-IMRT and 5-year DMFS was 78.8%. Prevertebral space invasion (PVS+) and N stage, but not T stage, were independent prognostic markers of DMFS (p = 0.016, < 0.001, and 0.433, respectively). Compared to stage N3, PVS invasion had a higher sensitivity (28.1 vs. 68.8%), but lower specificity (90.5 vs. 47.4%) and accuracy (76.7 vs. 48.9%) for correlating patients with DM. PVS invasion, together with parapharyngeal fat space invasion (PPFS+), was also an independent predictive marker of FEN+. CONCLUSION: PVS was the only site of primary tumour invasion that independently correlated with DM, and together with PPFS + was an independent prognostic marker of FEN+, but the low specificity and accuracy of PVS invasion limits its use as a prognostic marker of DM.

Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.

BACKGROUND: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice. METHODS: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. RESULTS: A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo-naive/post-chemo patients. In multivariate analysis, the presence of prostate-specific antigen (PSA) response (≥50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo-naive and post-chemo group. CONCLUSIONS: In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival.

Risk of acute myocardial infarction after androgen-deprivation therapy for prostate cancer in a Chinese population.

OBJECTIVE: To investigate the risk of acute myocardial infarction (AMI) after androgen-deprivation therapy (ADT) for prostate cancer in a Chinese population. PATIENTS AND METHODS: All Chinese patients with prostate cancer who were treated primarily with radical prostatectomy or radiotherapy, with or without further ADT at our hospital from the year 2000 to 2009 were retrospectively reviewed. We compared the risk of AMI in the patients who were given further ADT (ADT group) with those who were not given any ADT (non-ADT group). Potential risk factors of AMI including age, diabetes mellitus, hypertension, hyperlipidaemia, history of stroke, ischaemic heart disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and duration of ADT were reviewed. The risk of AMI after ADT was first analysed using the Kaplan-Meier method, followed by Cox regression analyses including the potential risk factors mentioned. RESULTS: In all, 452 patients were included, with 200 patients in the non-ADT group and 252 patients in the ADT group. The mean (sd) age was 68.2 (5.9) years in the non-ADT group and 69.5 (6.5) years in the ADT group, and the difference was statistically significant (P = 0.031). There were no significant differences in their pre-existing medical conditions or ECOG PS. The ADT group was associated with an increased risk of AMI when compared with the non-ADT group (P = 0.004) upon Kaplan-Meier analysis. Upon multivariate Cox regression analysis, hyperlipidaemia, poor ECOG PS and the use of ADT were the only three significant factors that were associated with increased risk of developing new AMI. CONCLUSIONS: There was increased risk of AMI after ADT for prostate cancer in a Chinese population. Hyperlipidaemia and poor ECOG PS were also significant risk factors for developing AMI. The risk of AMI should be considered when deciding on ADT, especially in patients with history of hyperlipidaemia and relatively poor ECOG PS.

Avelumab maintenance therapy for node-positive muscle invasive bladder cancer: a report of two cases.

Background: Muscle-invasive bladder cancer (MIBC) with nodal involvement is associated with poor prognosis and high mortality. Treatment of node-positive MIBC is complex due to disease heterogeneity and a lack of evidence-based treatment options, especially alternatives to radical cystectomy. We describe a bladder-sparing management approach involving systemic therapy followed by maintenance therapy, illustrated with two cases of node-positive MIBC. Case presentation: Two patients with node-positive MIBC received upfront gemcitabine/cisplatin chemotherapy, concurrent chemoradiotherapy (cCRT), and avelumab (immune checkpoint inhibitor) maintenance therapy. Both patients achieved complete remission without recurrence or distant metastasis post-avelumab maintenance therapy. At the last follow-up, Patient 1 (45-year-old male) was in remission for over two years, and Patient 2 (57-year-old male) was in complete remission for over one year post-chemotherapy. Avelumab treatment was well-tolerated, with no immune-related adverse events, and quality of life (QoL) was maintained. Conclusion: Both cases showed a good response and extended remission on avelumab maintenance, supporting its use in conjunction with local consolidation therapy as a bladder-preserving approach in node-positive MIBC. Further research, such as the ongoing INSPIRE trial, is required to refine treatment strategies for this patient group.

Prostate diffusion-weighted imaging (DWI) in MR-guided radiotherapy: Reproducibility assessment on 1.5 T MR-Linac and 1.5 T MR-simulator.

PURPOSE: Diffusion-weighted imaging (DWI) holds promise for image-guided radiotherapy (MRgRT) in prostate cancer. However, challenges persist due to image distortion, artifacts, and apparent diffusion coefficient (ADC) reproducibility issues. This study aimed to assess DWI image quality and ADC reproducibility on both a 1.5 T MR-simulator and a 1.5 T MR-Linac, employing measurements from both an ACR MRI phantom and prostate cancer patients undergoing MRgRT. METHODS: DW-MRI scans were conducted on 19 patients (mean age = 69 ± 8 years, with 23 MR-visible intra-prostatic lesions) and an ACR MRI phantom using a 1.5 T MR-simulator (b-values = 0, 800, 1400s/mm2) and a 1.5 T MR-Linac (b-values = 50, 500, 800 s/mm2). ADC homogeneity in the phantom was evaluated via 1D profile flatness (FL) in three directions. Image quality was assessed through qualitative 5-point Likert scale ratings and quantitative ADC and signal-to-noise ratio (SNR) measurements. Intra-observer reproducibility of image quality scores was evaluated using ICC(1, 2). Geometric distortion was measured by comparing landmark sizes on the ACR phantom against the ground truth. Mean ADC and reproducibility were assessed using Bland-Altman plots. RESULTS: Both MR-simulator and MR-Linac demonstrated high ADC homogeneity (FL > 87.5% - MR-simulator: 97.23 ± 0.62%, MR-Linac: 94.75 ± 0.62%, p < 0.05) in the phantom. Image quality scores revealed acceptable ratings (≥3) for capsule demarcation, image artifacts, and geometric distortion in patients. However, intra-prostatic lesions were barely discernible in b800 images for both MR-simulator (average score = 2.37 ± 1.33) and MR-Linac (average score = 2.16 ± 1.28). While MR-Linac DWI scans exhibited significantly more severe geometric distortion than MR-simulator scans (p < 0.01), most phantom measurements fell within the image in-plane resolution of 3 mm. Significant differences were noted in MR-simulator ADC (CTV: 1.20 ± 0.14 × 10-3 mm2/s (MR-simulator) vs 1.06 ± 0.10 × 10-3 mm2/s (MR-Linac); GTV: 1.05 ± 0.21 × 10-3 mm2/s vs 0.91 ± 0.16 × 10 mm2/s, all p < 0.05), with a small non-zero bias observed in the Bland-Altman analysis (CTV: 12.3%; GTV: 14.5%). CONCLUSION: The significantly larger MR-simulator ADC and the small non-zero bias hint at potential systematic differences in ADC values acquired from an MR-simulator and an MR-Linac, both at 1.5 T. Although acceptable ADC homogeneity was noted, caution is warranted in interpreting MR-Linac DWI images due to occasional severe artifacts. Further studies are essential to validate DWI and ADC as reliable imaging markers in prostate cancer MRgRT.

A territory-wide real-world efficacy and toxicity analysis of abiraterone acetate versus docetaxel in 574 Asian patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Abiraterone acetate (ABI) or docetaxel (DOC), in addition to androgen-deprivation therapy (ADT), are current treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). No randomized head-to-head trial has compared these 2 mHSPC treatments, and real-world data regarding their outcomes in Asian patients are lacking. PATIENTS AND METHODS: The medical records of mHSPC patients who began upfront ABI or DOC treatment in addition to ADT at seven public oncology centers in Hong Kong between 2015 and 2021 were reviewed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and toxicities. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: A total of 574 patients were included, of whom 419 received DOC and 155 received ABI. The median follow-up duration was 22.4 (DOC group: 23.8; ABI group: 17.3) months. The ABI group demonstrated significantly better PFS than the DOC group (not reached vs. 15.1 months: hazard ratio = 0.37; 95% confidence interval = 0.28-0.50; P < .001). No significant OS difference was observed (P = .58). Failure to achieve a ≥ 90% decline in PSA level at 3 months and failure to achieve an undetectable PSA nadir were each associated with unfavorable PFS and OS. Patients who received DOC had a higher rate of febrile neutropenia, whereas those who received ABI had higher rates of grade ≥ 3 hypokalemia and elevated alanine transaminase. Treatment discontinuation due to toxicities was more common in the DOC (3.6%) than the ABI (0.6%) group. CONCLUSION: In Asian mHSPC patients, upfront ABI + ADT was associated with better PFS than DOC + ADT, with no significant OS difference. PSA kinetics may help stratify the prognosis for treatment intensification. Toxicity profiles were different, with a higher rate of toxicity-related treatment discontinuation in the DOC group.

Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Evaluation of the Reliability and the Performance of Magnetic Resonance Imaging Radiomics in the Presence of Randomly Generated Irrelevant Features for Prostate Cancer.

Radiomics has the potential to aid prostate cancer (PC) diagnoses and prediction by analyzing and modeling quantitative features extracted from clinical imaging. However, its reliability has been a concern, possibly due to its high-dimensional nature. This study aims to quantitatively investigate the impact of randomly generated irrelevant features on MRI radiomics feature selection, modeling, and performance by progressively adding randomly generated features. Two multiparametric-MRI radiomics PC datasets were used (dataset 1 (n = 260), dataset 2 (n = 100)). The endpoint was to differentiate pathology-confirmed clinically significant (Gleason score (GS) ≥ 7) from insignificant (GS < 7) PC. Random features were generated at 12 levels with a 10% increment from 0% to 100% and an additional 5%. Three feature selection algorithms and two classifiers were used to build the models. The area under the curve and accuracy were used to evaluate the model's performance. Feature importance was calculated to assess features' contributions to the models. The metrics of each model were compared using an ANOVA test with a Bonferroni correction. A slight tendency to select more random features with the increasing number of random features introduced to the datasets was observed. However, the performance of the radiomics-built models was not significantly affected, which was partially due to the higher contribution of radiomics features toward the models compared to the random features. These reliability effects also vary among datasets. In conclusion, while the inclusion of additional random features may still slightly impact the performance of the feature selection, it may not have a substantial impact on the MRI radiomics model performance.