Magnetic Resonance Imaging-Derived biomarkers of Isocitrate-Dehydrogenase mutation in diffuse gliomas: a conventional MR and Diffusion Weighted Imaging study.

The introduction of molecular criteria into the classification of diffuse gliomas has added interesting practical implications to glioma management. This has created a new clinical need for correlating imaging characteristics with glioma genotypes, also known as radiogenomics or imaging genomics. Whilst many studies have primarily focused on the use of advanced magnetic resonance imaging (MRI) techniques for radiogenomics purposes, conventional MRI sequences still remain the reference point in the study and characterization of brain tumours. Moreover, a different approach may rely on diffusion-weighted imaging (DWI) usage, which is considered a “conventional” sequence in line with recently published directions on glioma imaging. In a non-invasive way, it can provide direct insight into the microscopic physical properties of tissues. Considering that Isocitrate-Dehydrogenase gene mutations may reflect alterations in metabolism, cellularity, and angiogenesis, which may manifest characteristic features on an MRI, the identification of specific MRI biomarkers could be of great interest in managing patients with brain gliomas. My study aimed to evaluate the presence of specific MRI-derived biomarkers of IDH molecular status through conventional MRI and DWI sequences.

Spazi postcoloniali: dislocazioni, diaspore, cartografie

La presente tesi di dottorato si propone di ricostruire criticamente la riflessione postcoloniale sullo spazio, riconoscendo nella critica postcoloniale l’introduzione di una fondamentale interrogazione degli spazi che sviluppa cartografie concettuali originali. Il lavoro si concentra sulla duplice operazione svolta dagli studi postcoloniali rispetto al tema degli spazi, riguardando, da una parte, le istanze critiche volte a condannare e contraddire le diverse spazialità del dominio coloniale; dall’altra, elaborando in risposta delle alternative concettuali forti, tali da offrire nuove immagini e strumenti per ripensare in modo abilitante gli spazi politici per il presente globale. Rispecchiando questo duplice indirizzo, la tesi si divide in due parti, precedute da un capitolo introduttivo, volto a presentare una strategia di fondo del pensiero postcoloniale sugli spazi, quella di un "entanglement" atto a ingarbugliare produttivamente fra loro le spazialità sottoposte a divisione e segregazione da parte del dominio coloniale (capitolo 1). A seguire, una pars destruens indaga la contestazione postcoloniale di specifiche spazialità coloniali, (capitolo 2); e discute la critica postcoloniale mossa alla geografia e alla cartografia moderne, in quanto strumenti di potere/sapere coloniale, atti alla costruzione di uno spazio globale strutturalmente asimmetrico, a cui consegue però, da parte postcoloniale, l’elaborazione di contro-cartografie critiche (capitolo 3). Segue una pars construens, dedicata a due concetti-chiave della riflessione postcoloniale sullo spazio, ovvero il pianeta, indagato come “sovrascrittura del globo”, la riflessione sul quale inoltre si fa occasione, da parte del pensiero postcoloniale, per intercettare istanze ecologiche urgenti e, insieme, riflettere sul problema del cosmopolitismo (capitolo 4); e il confine, la cui ricca e complessa ri-significazione in una prospettiva postcoloniale viene qui ricostruita nelle sue molte dimensioni (capitolo 5). Seguono delle conclusioni a fare un riassunto e un bilancio degli argomenti così ripercorsi, mettendo in luce in particolare i temi della dislocazione, della diaspora e della traduzione.

Anatomical biomarkers of body composition in oncological population: application and development of artificial intelligences

In the Era of precision medicine and big medical data sharing, it is necessary to solve the work-flow of digital radiological big data in a productive and effective way. In particular, nowadays, it is possible to extract information “hidden” in digital images, in order to create diagnostic algorithms helping clinicians to set up more personalized therapies, which are in particular targets of modern oncological medicine. Digital images generated by the patient have a “texture” structure that is not visible but encrypted; it is “hidden” because it cannot be recognized by sight alone. Thanks to artificial intelligence, pre- and post-processing software and generation of mathematical calculation algorithms, we could perform a classification based on non-visible data contained in radiological images. Being able to calculate the volume of tissue body composition could lead to creating clasterized classes of patients inserted in standard morphological reference tables, based on human anatomy distinguished by gender and age, and maybe in future also by race. Furthermore, the branch of “morpho-radiology" is a useful modality to solve problems regarding personalized therapies, which is particularly needed in the oncological field. Actually oncological therapies are no longer based on generic drugs but on target personalized therapy. The lack of gender and age therapies table could be filled thanks to morpho-radiology data analysis application.

Hypofractionated stereotactic radiotherapy after hyperbaric oxygenation for recurrent high-grade glioma: a pilot study

Purpose The presence of hypoxic cells in high-grade glioma (HGG) is one of the main reasons of local failure after radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of hypoxia in poorly oxygenated regions of the tumor. We performed a pilot study to evaluate the efficacy of hypofractionated image-guided helical TomoTherapy (HT) after HBO in the treatment of recurrent HGG (rHGG). Methods We enrolled 15 patients (aged >18 years) with diagnosis of rHGG. A total dose of 15-25 Gy was administered in daily 5-Gy fractions for 3-5 consecutive days after daily HBO. Each fraction was delivered up to maximum of 60 minutes after HBO. Results Median follow-up from HBO-RT was 28.6 (range: 5.3-56.8). No patient was lost to follow-up. Median progression-free survival (mPFS) for all patients was 3.2 months (95% CI: 1.34- 6.4 ), while 3-month, 6-month and 12 month PFS was 60% (95%CI: 31.8.4-79.7), 40% (95%CI: 16.5- 62.8) and10.0 (0.8-33.5) , respectively. Median overall survival (mOS) of HBO-RT was 11.7 months (95% CI: 7.3-29.3), while 3-month, 6-month and 12 month OS was 100% , 93.3% (61.3-99.0) and 46.7 % (21.2-68.8). No acute or late neurologic toxicity >grade 2 (CTCAE version 4.3) was observed in 86.66% of patients. Two patients developed G3 Radionecrosis. Conclusion HSRT combined to HBO seems effective and safe in the treatment of rHGG. One of advantages of HBO-RT is the reduced overall treatment time (3-5 consecutive days).

Impatto dell'uso dell'Edmonton Symptom Assessment System all'interno di un ambulatorio integrato di radioterapia e cure palliative sull'ottimizzazione della qualita di cura

I pazienti affetti da patologie oncologiche avanzate hanno un'esperienza di sintomi multipli spesso concomitanti tra loro. Lo scopo di questo progetto è quello di valutare come, nel contesto di un’ambulatorio integrato di Radioterapia e Cure Palliative (rep), sia possibile descrivere e quantificare i sintomi riportati dal paziente attraverso uno strumento di analisi convalidato, nello specifico l’Edmonton Symptom Assessment System (ESAS) al fine di costruire una proposta terapeutica ottimizzata per il singolo paziente. Da aprile 2016 ad aprile 2020, sono stati analizzati gli accessi al rep per un totale di 519 accessi, quindi abbiamo selezionato solo le visite dei pazienti che avevano completato totalmente lo strumento ESAS per la valutazione dei sintomi. La popolazione in studio era quindi composta da 212 pazienti, di questi 120 erano uomini, 92 erano donne, l'età media era di 72 anni, del totale il 36% era stato sottoposto a radioterapia. I principali risultati ottenuti dall'analisi dei dati relativi alla popolazione in studio sono stati i seguenti: 1) il 25% dei pazienti muore entro 2,2 mesi, il 60% entro 6 mesi; 2) la popolazione maschile ha un rischio di morte più elevato rispetto alla popolazione femminile; 3) Esiste una chiara differenza negli indici di correlazione tra la popolazione femminile e quella maschile 4) I principali sintomi correlati sono: dolore, mancanza di appetito, ansia, sonnolenza; 5) Il sintomo del dolore non è associato ad un aumento del rischio di morte, mentre la mancanza di appetito e sonnolenza sono associati ad un aumento del rischio di morte. In conclusione, i dati a nostra disposizione hanno dimostrato che un'analisi approfondita dei sintomi attraverso lo strumento ESAS è fattibile e necessaria portando informazioni fondamentali per una gestione ottimale del paziente, dandoci la possibilità di muoverci verso l'opportunità di trattamenti sempre più personalizzati e individualizzati in base alle caratteristiche dei singoli pazienti.

Ultra-hypofractionated stereotactic radiotherapy for prostate cancer in 5 fractions: current evidences and our clinical experience

AIMS: The present is a retrospective evaluation of acute genito-urinary (GU) and gastro-intestinal (GI) toxicity, in addition to biochemical recurrence rate in 57 prostate cancer patients treated at our Institution with ultra-hypofractionated RT (UHRT) schedule. METHODS: From January 2021 to December 2022 we have treated 57 patients with prostate cancer, using an UHRT scheme of 5-fractions every other day for a total dose delivered of 36.25 Gy, according to the PACE-B trial treatment schedule. Good urinary function, assessed by International Prostate Symptom Score (IPSS), were required. The simulation CT scans were acquired in supine position and fused with MRI for CTVs definition for every patient. Each treatment was performed by Accuray's TomoTherapy with daily IGRT. The evaluation of the set-up was very restrictive before daily treatment delivery. RESULTS: According to RTOG toxicity scale, the acute GU toxicity at 3 months from RT, GU toxicity was G0 for 30 patients (52.6%), G1 for 26 (45.6%) and G2 for one only (1.75%); rectal toxicity was G0 for 56 patients (98.25%) and G1 for one only (1.75%). The median follow-up (FU) was 9 months (2-24 months). In the following FU months, we observed progressively lower urinary and rectal toxicity, except for one patient who showed G2 GU toxicity at 12 months. All but one patient had a progressive PSA value decrease. CONCLUSIONS: In our experience, UHRT appears to be safe and well tolerated even without the use of rectal spacer devices. A longer FU is necessary to evaluate late toxicity and disease control rate.

Developing a radiomic based machine learning model to identify patients with resected non-small-cell lung cancer at high risk of relapse

Background There is a wide variation of recurrence risk of Non-small-cell lung cancer (NSCLC) within the same Tumor Node Metastasis (TNM) stage, suggesting that other parameters are involved in determining this probability. Radiomics allows extraction of quantitative information from images that can be used for clinical purposes. The primary objective of this study is to develop a radiomic prognostic model that predicts a 3 year disease free-survival (DFS) of resected Early Stage (ES) NSCLC patients. Material and Methods 56 pre-surgery non contrast Computed Tomography (CT) scans were retrieved from the PACS of our institution and anonymized. Then they were automatically segmented with an open access deep learning pipeline and reviewed by an experienced radiologist to obtain 3D masks of the NSCLC. Images and masks underwent to resampling normalization and discretization. From the masks hundreds Radiomic Features (RF) were extracted using Py-Radiomics. Hence, RF were reduced to select the most representative features. The remaining RF were used in combination with Clinical parameters to build a DFS prediction model using Leave-one-out cross-validation (LOOCV) with Random Forest. Results and Conclusion A poor agreement between the radiologist and the automatic segmentation algorithm (DICE score of 0.37) was found. Therefore, another experienced radiologist manually segmented the lesions and only stable and reproducible RF were kept. 50 RF demonstrated a high correlation with the DFS but only one was confirmed when clinicopathological covariates were added: Busyness a Neighbouring Gray Tone Difference Matrix (HR 9.610). 16 clinical variables (which comprised TNM) were used to build the LOOCV model demonstrating a higher Area Under the Curve (AUC) when RF were included in the analysis (0.67 vs 0.60) but the difference was not statistically significant (p=0,5147).