THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy

Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Modern Management of Esophageal Cancer: Radio-Oncology in Neoadjuvancy, Adjuvancy and Palliation

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

Contrast enhanced spectral mammography (CESM) guided breast biopsy as an alternative to MRI guided biopsy

Objective: Contrast Enhanced Spectral Mammography (CESM) breast biopsy has been recently introduced into clinical practice. This short communication describes the technique and potential as an alternative to MRI guided biopsy. Methods and materials: An additional abnormality was detected on a breast MRI examination in a patient with lobular carcinoma. The lesion was occult on conventional mammography, tomosynthesis and ultrasound and required histological diagnosis. Traditionally this would have necessitated a MRI guided breast biopsy, but was performed under CESM guidance. Results: A diagnostic CESM study was performed to ensure the lesion visibility with CESM and then targeted under CESM guidance. A limited diagnostic study, CESM scout and paired images for stereotactic targeting were obtained within a 10 min window following a single injection of iodinated contrast agent. The time from positioning in the biopsy device to releasing compression after biopsy and marker clip placement was 15 min. The biopsy confirmed the presence of multifocal breast cancer. Conclusion: CESM guided breast biopsy is a new technique that can be successfully used as an alternative to MRI guided breast biopsy. Advances in knowledge: CESM guided biopsy can be used to sample breast lesions which remain occult on standard mammography and ultrasound.

Tumor microenvironment responsive self-cascade catalysis for synergistic chemo/chemodynamic therapy by multifunctional biomimetic nanozymes

Multifunctional biomimetic nanozyme (SSMA/DOX) is fabricated, which enables tumor microenvironment responsive self-cascade catalysis to reach MRI guided enhanced chemo/chemodynamic therapy.

Validation of PI-RADS v2 Scores at Various Non-University Radiology Practices

Purpose: The purpose of this study was to validate the second version of the Prostate Imaging Reporting and Data System (PI-RADSv2) scores in predicting positive in-bore MRI-guided targeted prostate biopsy results across different non-university related institutions. The study focuses on PI-RADS v2 scoring because during the study period, PI-RADS v2.1 had not been released. Materials and Methods: This was a retrospective review of 147 patients who underwent multiparametric magnetic resonance imaging (mpMRI) of the pelvis followed by in-bore MRI-guided targeted prostate biopsy from December 2014 to May 2018. All lesions on mpMRI were rated according to PI-RADS v2 criteria. PI-RADS v2 scores were then compared to MR-guided biopsy results and pre-biopsy PSA values. Results: Prostate Cancer (PCa) was detected in 54% (80/147) of patients, with more prostate cancer being detected with each subsequent increase in PI-RADS scores. Specifically, biopsy results in patients with PI-RADS 3, 4, and 5 lesions resulted in PCa in 25.6% (10/39), 58.1% (33/55), and 86.0% (37/43) respectively. Clinically significant PCa (Gleason score ≥7) was detected in 17.9% (7/39), 52.7% (29/55), and 72% (31/43) of cases for PI-RADS 3, 4, and 5 lesions respectively. When the PI-RADS scoring and biopsy results were compared across different institutions, there was no difference in the PI-RADS scoring of lesions or in the positive biopsy rates of the lesions. The sensitivity, specificity, PPV, and NPV for PI-RADS 3-4 lesions were also not statistically different across the institutions for detecting Gleason 7 or greater lesions. Conclusion: Our results agree with prior studies that higher PI-RADS scores are associated with the presence of clinically significant PCa and suggest prostate lesions with PI-RADS scores 3-5 have sufficient evidence to warrant targeted biopsy. The comparison of PI-RADS score across different types of non-university practices revealed no difference in scoring and biopsy outcome, suggesting that PI-RADS v2 can be easily applied outside of the university medical center setting. Clinical Relevance: PI-RADS v2 can be applied homogeneously in the non-university setting without significant difference in outcome.