A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols.

BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS: We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS: A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS: The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.

Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has greater specificity and sensitivity for detection of extraprostatic prostate cancer (PCa) at presentation than conventional imaging. Although the long-term clinical significance of acting on these findings is unknown, it has been shown that the risk of upstaging is prognostic for long-term outcomes in men with high-risk (HR) or very high-risk (VHR) PCa. We evaluated the association between the risk of upstaging on PSMA PET and the Decipher genomic classifier score, a known prognostic biomarker in localized PCa that is being evaluated for its predictive ability to direct systemic therapy intensification. In a cohort of 4625 patients with HR or VHR PCa, the risk of upstaging on PSMA PET was significantly correlated with the Decipher score (p < 0.001). These results should be seen as hypothesis-generating and warrant further studies on the causal pathways linking PSMA findings, Decipher scores, extraprostatic disease, and long-term clinical outcomes. PATIENT SUMMARY: We found significant correlation between the risk of having prostate cancer outside the prostate gland on a sensitive scan (based on prostate-specific membrane antigen [PSMA]) at initial staging and the Decipher genetic score. The results warrant further studies on the causal pathways between PSMA scan findings, Decipher scores, disease outside the prostate, and long-term outcomes.

Brief Report: Severe Pneumonitis After Combined Thoracic Radiotherapy and Osimertinib.

Introduction: Osimertinib is an effective treatment for metastatic NSCLC. Occasionally, thoracic radiation therapy (TRT) is delivered to patients receiving osimertinib to treat residual or progressing pulmonary tumors. Anecdotal reports suggest that the delivery of TRT in combination with osimertinib may be associated with a high risk of severe pneumonitis. Methods: A retrospective study was performed at a single academic medical center in the United States to investigate the incidence of severe pneumonitis among patients treated with combined TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of radiation pneumonitis that developed within 6 months of treatment was scored in accordance with the Common Terminology Criteria for Adverse Events version 5.0. Results: A total of 16 patients were identified who were treated with combined TRT and osimertinib. All had a diagnosis of metastatic NSCLC. Treatment-related grade greater than or equal to 2 pneumonitis developed in 56%, grade greater than or equal to 3 in 37.5%, and grade 4 in 6.3%; no patient developed grade 5 pneumonitis. Median time to any-grade pneumonitis was 29 days (1-84 d); all patients had symptom resolution with expectant management or oral steroid therapies. All patients discovered to have grade greater than or equal to 3 pneumonitis (n = 6) received TRT to tumors located within 2 cm of the proximal bronchial tree, including tumors abutting the proximal bronchial tree (n = 2) and within the mediastinum (n = 1). Conclusions: The combination of TRT with osimertinib was associated with a high rate of severe pneumonitis that required oral steroid medications. Larger studies are needed to validate these findings and to understand the clinical and treatment factors that influence this risk and how they can be mitigated.

Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma.

INTRODUCTION: The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT. METHODS: This study used a cost-effectiveness Markov model simulating 5 year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of ABVD chemotherapy ± ISRT or CMT consisting of 2 cycles of ABVD + ISRT. Patients progressed to no evidence of disease, progression of disease (PD), or death. Patients with PD underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). The primary outcome measured was the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were performed. RESULTS: We found that PET-directed therapy and CMT strategies were associated with costs of $47,362 and $41,167, respectively. The CMT strategy was equally as effective as the PET-directed therapy strategy with QALYs of 3.4. On 1-way sensitivity analyses, the model was most sensitive to CMT and HDC-SCT costs. Two-way sensitivity analyses showed the model was sensitive to the relative costs of these treatments. CONCLUSION: For patients with early-stage HL, CMT is the cost-effective strategy as compared with PET-directed therapy.

Local failure after definitive radiation treatment of lymph-node positive prostate cancer: supporting the use of novel imaging techniques to personalize treatment options.

Patients with lymph-node positive prostate cancer are often treated with external beam radiotherapy with androgen deprivation therapy1, but are expected to have a high rate of biochemical failure. Recently, MRI and molecular imaging have afforded the opportunity to elucidate otherwise occult sites of recurrence after conventional imaging. We present an unusual case of local failure within the prostate after definitive radiation treatment of lymph-node positive prostate cancer, in which advanced imaging allowed for a potentially curative salvage treatment option.

Multicenter Multireader Evaluation of an Artificial Intelligence-Based Attention Mapping System for the Detection of Prostate Cancer With Multiparametric MRI.

OBJECTIVE. The purpose of this study was to evaluate in a multicenter dataset the performance of an artificial intelligence (AI) detection system with attention mapping compared with multiparametric MRI (mpMRI) interpretation in the detection of prostate cancer. MATERIALS AND METHODS. MRI examinations from five institutions were included in this study and were evaluated by nine readers. In the first round, readers evaluated mpMRI studies using the Prostate Imaging Reporting and Data System version 2. After 4 weeks, images were again presented to readers along with the AI-based detection system output. Readers accepted or rejected lesions within four AI-generated attention map boxes. Additional lesions outside of boxes were excluded from detection and categorization. The performances of readers using the mpMRI-only and AI-assisted approaches were compared. RESULTS. The study population included 152 case patients and 84 control patients with 274 pathologically proven cancer lesions. The lesion-based AUC was 74.9% for MRI and 77.5% for AI with no significant difference (p = 0.095). The sensitivity for overall detection of cancer lesions was higher for AI than for mpMRI but did not reach statistical significance (57.4% vs 53.6%, p = 0.073). However, for transition zone lesions, sensitivity was higher for AI than for MRI (61.8% vs 50.8%, p = 0.001). Reading time was longer for AI than for MRI (4.66 vs 4.03 minutes, p < 0.001). There was moderate interreader agreement for AI and MRI with no significant difference (58.7% vs 58.5%, p = 0.966). CONCLUSION. Overall sensitivity was only minimally improved by use of the AI system. Significant improvement was achieved, however, in the detection of transition zone lesions with use of the AI system at the cost of a mean of 40 seconds of additional reading time.

Novel Imaging in Detection of Metastatic Prostate Cancer.

PURPOSE OF REVIEW: This review aims to highlight the limitations of current standard-of-care prostate cancer (PCa) imaging and discuss novel clinical imaging in advanced disease. RECENT FINDINGS: PCa staging through imaging is important for proper selections in clinical treatment. Traditional imaging techniques for metastatic disease (i.e., computed tomography [CT], magnetic resonance imaging [MRI], and radionuclide bone scan) have suboptimal performance in early recurrent or metastatic disease. Novel positron emission tomography agents including radiolabeled prostate specific membrane antigen (PSMA), choline, and anti-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) have demonstrated improved sensitivity and specificity in initial staging and early biochemical recurrence (BCR). Conventional imaging modalities for PCa incompletely characterize disease burden. The development of new PET tracers in combination with CT and MRI offers superior anatomic localization and biologic correlation of tumor sites, which enhance providers' abilities to make appropriate decisions regarding treatment.

Radiomics and radiogenomics of prostate cancer.

Radiomics and radiogenomics are attractive research topics in prostate cancer. Radiomics mainly focuses on extraction of quantitative information from medical imaging, whereas radiogenomics aims to correlate these imaging features to genomic data. The purpose of this review is to provide a brief overview summarizing recent progress in the application of radiomics-based approaches in prostate cancer and to discuss the potential role of radiogenomics in prostate cancer.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. METHODS: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. RESULTS: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. CONCLUSIONS: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Intra- and interreader reproducibility of PI-RADSv2: A multireader study.

BACKGROUND: The Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) has been in use since 2015; while interreader reproducibility has been studied, there has been a paucity of studies investigating the intrareader reproducibility of PI-RADSv2. PURPOSE: To evaluate both intra- and interreader reproducibility of PI-RADSv2 in the assessment of intraprostatic lesions using multiparametric magnetic resonance imaging (mpMRI). STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 102 consecutive biopsy-naïve patients who underwent prostate MRI and subsequent MR/transrectal ultrasonography (MR/TRUS)-guided biopsy. FIELD STRENGTH/SEQUENCES: Prostate mpMRI at 3T using endorectal with phased array surface coils (TW MRI, DW MRI with ADC maps and b2000 DW MRI, DCE MRI). ASSESSMENT: Previously detected and biopsied lesions were scored by four readers from four different institutions using PI-RADSv2. Readers scored lesions during two readout rounds with a 4-week washout period. STATISTICAL TESTS: Kappa (κ) statistics and specific agreement (Po ) were calculated to quantify intra- and interreader reproducibility of PI-RADSv2 scoring. Lesion measurement agreement was calculated using the intraclass correlation coefficient (ICC). RESULTS: Overall intrareader reproducibility was moderate to substantial (κ = 0.43-0.67, Po = 0.60-0.77), while overall interreader reproducibility was poor to moderate (κ = 0.24, Po = 46). Readers with more experience showed greater interreader reproducibility than readers with intermediate experience in the whole prostate (P = 0.026) and peripheral zone (P = 0.002). Sequence-specific interreader agreement for all readers was similar to the overall PI-RADSv2 score, with κ = 0.24, 0.24, and 0.23 and Po = 0.47, 0.44, and 0.54 in T2 -weighted, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE), respectively. Overall intrareader and interreader ICC for lesion measurement was 0.82 and 0.71, respectively. DATA CONCLUSION: PI-RADSv2 provides moderate intrareader reproducibility, poor interreader reproducibility, and moderate interreader lesion measurement reproducibility. These findings suggest a need for more standardized reader training in prostate MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2.

Evaluating the size criterion for PI-RADSv2 category 5 upgrade: is 15 mm the best threshold?

PURPOSE: The purpose of the study was to determine if the ≥ 15 mm threshold currently used to define PIRADS 5 lesions is the optimal size threshold for predicting high likelihood of clinically significant (CS) cancers. MATERIALS: Three hundred and fifty-eight lesions that may be changed from category 4 to 5 or vice versa on the basis of the size criterion (category 4: n = 288, category 5: n = 70) from 255 patients were evaluated. Kendall's tau-b statistic accounting for inter-lesion correlation, generalized estimation equation logistic regression, and receiver operating curve analysis evaluated two lesion size-metrics (lesion diameter and relative lesion diameter-defined as lesion diameter/prostate volume) for ability to identify CS (Gleason grade ≥ 3 + 4) cancer at targeted biopsy. Optimal cut-points were identified using the Youden index. Analyses were performed for the whole prostate (WP) and zone-specific sub-cohorts of lesions in the peripheral and transition zones (PZ and TZ). RESULTS: Lesion diameter showed a modest correlation with Gleason grade (WP: τB = 0.21, p < 0.0001; PZ: τB = 0.13, p = 0.02; TZ: τB = 0.32, p = 0.001), and association with CS cancer detection (WP: AUC = 0.63, PZ: AUC = 0.59, TZ: AUC = 0.74). Empirically derived thresholds (WP: 14 mm, PZ: 13 mm, TZ: 16 mm) performed similarly to the current ≥ 15 mm standard. Lesion relative lesion diameter improved identification of CS cancers compared to lesion diameter alone (WP: τB = 0.30, PZ: τB = 0.24, TZ: τB = 0.42, all p < 0.0001). AUC also improved for WP and PZ lesions (WP: AUC = 0.70, PZ: AUC = 0.68, and TZ: AUC = 0.74). CONCLUSIONS: The current ≥ 15 mm diameter threshold is a reasonable delineator of PI-RADS category 4 and category 5 lesions in the absence of extraprostatic extension to predict CS cancers. Additionally, relative lesion diameter can improve identification of CS cancers and may serve as another option for distinguishing category 4 and 5 lesions.

PI-RADS v2: Current standing and future outlook.

The Prostate Imaging-Reporting and Data System (PI-RADS) was created in 2012 to establish standardization in prostate multiparametric magnetic resonance imaging (mpMRI) acquisition, interpretation, and reporting. In hopes of improving upon some of the PI-RADS v1 shortcomings, the PI-RADS Steering Committee released PI-RADS v2 in 2015. This paper reviews the accuracy, interobserver agreement, and clinical outcomes of PI-RADS v2 and comments on the limitations of the current literature. Overall, PI-RADS v2 shows improved sensitivity and similar specificity compared to PI-RADS v1. However, concerns exist regarding interobserver agreement and the heterogeneity of the study methodology.

Patient-Reported Sexual Aid Utilization and Efficacy After Radiation Therapy for Localized Prostate Cancer.

PURPOSE: To report sexual health-related quality of life outcomes and utilization and efficacy of sexual aids in a contemporary cohort of patients treated for localized prostate cancer. PATIENTS AND METHODS: Between 2008 and 2013, 471 consecutive men with localized prostate cancer were treated on 2 institutional protocols (NCT01766492, NCT01618851) or on a prospective institutional registry with patient-reported health-related quality of life. All patients were treated with ultra-hypofractionated radiation therapy. Erectile function (EF) was defined as "firm enough for intercourse" with or without aids per Expanded Prostate Cancer Index Composite-26 (n = 222 at baseline); results apply to this cohort unless specifically noted. Sexual aid utilization and efficacy were patient reported. Multivariable analysis of EF was performed. RESULTS: Median follow-up was 60 months, median age was 67 years, and 70% had intermediate- or high-risk disease per National Comprehensive Cancer Network guidelines. At 24 and 60 months, questionnaire response rates were 86% and 67%, and EF was retained in 53% and 41%, respectively. Baseline sexual aid utilization was 37% (n = 82) and was associated with lower 24-month EF preservation on multivariable analysis (adjusted odds ratio 0.49, 95% confidence interval 0.26-0.92). By 60 months, 70% of men had tried aids. Of those who found aids helpful at baseline, 84% to 89% reported continued benefit at 24 to 60 months. Among aid-naïve patients, efficacy was 80% with first-time use within 12 months and 70% more than 12 months after radiation therapy (P = .02). Among men who developed erectile dysfunction but found sexual aids helpful, 25% were not current users at 60 months. CONCLUSIONS: One-third of men used sexual aids at baseline, which doubled by 5 years after radiation therapy. Self-reported efficacy was high and sustained. Despite significant declines in EF, a number of men reported helpfulness of aids but were not active users. Future study is required to understand drivers of aid utilization to optimize posttreatment sexual function.