The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer.

BACKGROUND: MYC is a commonly amplified, potentially targetable gene in prostate cancer (PCa). We sought to define the molecular, immunologic, and clinicodemographic landscape of MYC amplification (MYCamp) in advanced PCa to establish a rationale for personalized treatment combinations. METHODS: Hybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples. MYCamp = copy number ≥6 (CN). Patients treated between January 2011 and December 2020 were selected from a nationwide deidentified (280 clinics) EHR-derived clinicogenomic database (CGDB). RESULTS: Of 12,528 hormone-sensitive and castrate-resistant (CRPC) samples, MYCamp was detected in 10.6% (median CN = 8). MYCamp was more frequent in men with African versus European ancestry (12.9% vs. 10.2% P = .002), in metastatic vs. primary tissue (15.7% vs. 6.2% P < .001), and enriched in metastatic liver lesions (20.2%), but inversely associated with high microsatellite-instability (0.8% vs. 2.4%, P < .001). MYC CN≥15 was associated with PD-L1 expression (26.1% vs. 9.8%, P = .025). Amplification of AR, RAD21, LYN, CCND1, ZNF703, FGF3/4/19, and FGFR1 was enriched in MYCamp vs. MYCwt (all P < .001). In liquid samples with tumor fraction [TF]>0, MYCamp was detected in 2.0% (28/1,402), and 4.5% (20/445) with TF>20%. In the CGDB, (67 MYCamp and 658 MYCwt), patients received similar treatments; most received hormone therapies (35.8% MYCamp vs. 31.5% MYCwt) or chemotherapy (37.3% MYCamp vs. 27.7% MYCwt) as first therapy after CGP report. CONCLUSION: MYCamp defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYCamp may be prognostic; independent cohorts are needed to validate these findings.

MRI-based delta-radiomic features for prediction of local control in liver lesions treated with stereotactic body radiation therapy.

Real-time magnetic resonance image guided stereotactic ablative radiotherapy (MRgSBRT) is used to treat abdominal tumors. Longitudinal data is generated from daily setup images. Our study aimed to identify delta radiomic texture features extracted from these images to predict for local control in patients with liver tumors treated with MRgSBRT. Retrospective analysis of an IRB-approved database identified patients treated with MRgSBRT for primary liver and secondary metastasis histologies. Daily low field strength (0.35 T) images were retrieved, and the gross tumor volume was identified on each image. Next, images' gray levels were equalized, and 39 s-order texture features were extracted. Delta-radiomics were calculated as the difference between feature values on the initial scan and after delivered biological effective doses (BED, α/ß = 10) of 20 Gy and 40 Gy. Then, features were ranked by the Gini Index during training of a random forest model. Finally, the area under the receiver operating characteristic curve (AUC) was estimated using a bootstrapped logistic regression with the top two features. We identified 22 patients for analysis. The median dose delivered was 50 Gy in 5 fractions. The top two features identified after delivery of BED 20 Gy were gray level co-occurrence matrix features energy and gray level size zone matrix based large zone emphasis. The model generated an AUC = 0.9011 (0.752-1.0) during bootstrapped logistic regression. The same two features were selected after delivery of a BED 40 Gy, with an AUC = 0.716 (0.600-0.786). Delta-radiomic features after a single fraction of SBRT predicted local control in this exploratory cohort. If confirmed in larger studies, these features may identify patients with radioresistant disease and provide an opportunity for physicians to alter management much sooner than standard restaging after 3 months. Expansion of the patient database is warranted for further analysis of delta-radiomic features.

A Review of Boron Neutron Capture Therapy: Its History and Current Challenges.

Mechanism of Action: External beam, whether with photons or particles, remains as the most common type of radiation therapy. The main drawback is that radiation deposits dose in healthy tissue before reaching its target. Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when 10B is irradiated with low-energy (0.0025 eV) thermal neutrons. The resulting 10B(n,α)7Li capture reaction produces high linear energy transfer (LET) α particles, helium nuclei (4He), and recoiling lithium-7 (7Li) atoms. The short range (5-9 µm) of the α particles limits the destructive effects within the boron-containing cells. In theory, BNCT can selectively destroy malignant cells while sparing adjacent normal tissue at the cellular levels by delivering a single fraction of radiation with high LET particles. History: BNCT has been around for many decades. Early studies were promising for patients with malignant brain tumors, recurrent tumors of the head and neck, and cutaneous melanomas; however, there were certain limitations to its widespread adoption and use. Current Limitations and Prospects: Recently, BNCT re-emerged owing to several developments: (1) small footprint accelerator-based neutron sources; (2) high specificity third-generation boron carriers based on monoclonal antibodies, nanoparticles, among others; and (3) treatment planning software and patient positioning devices that optimize treatment delivery and consistency.