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Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.

We report on the early clinical outcomes of a prospective series of early breast cancer (EBC) patients treated with ultra-hypofractionated post-operative whole-breast irradiation (WBI) after breast-conserving surgery (BCS) and axillary management. Primary endpoints were patient’s compliance and acute toxicity. Secondary endpoints included physician-rated cosmesis and ipsilateral breast tumour recurrence (IBTR). Acute toxicity was evaluated at the end of WBI, 3 weeks and 6 months thereafter, according to the Common Terminology Criteria for Adverse Events (v. 5.0). Patients were treated between September 2021 and May 2022. The treatment schedule for WBI consisted of either 26 Gy in 5 fractions over one week (standard approach) or 28.5 Gy in 5 fractions over 5 weeks (reserved to elders). Inverse planned intensity-modulated radiation therapy (IMRT) was used employing a static technique. A total of 70 patients were treated. Fifty-nine were treated with the 26 Gy/5 fr/1 w and 11 with the 28.5 Gy/5 fr/5 ws schedule. Median age was 67 and 70 in the two groups. Most of the patients had left-sided tumours (53.2%) in the 26 Gy/5 fr/1 w or right-sided lesions (63.6%) in the 28.5 Gy/5 fr/5 ws group. Most of the patients had a clinical T1N0 disease and a pathological pT1pN0(sn) after surgery. Ductal invasive carcinoma was the most frequent histology. Luminal A intrinsic subtyping was most frequent. Most of the patients underwent BCS and sentinel lymph node biopsy and adjuvant endocrine therapy. All patients completed the treatment program as planned. Maximum detected acute skin toxicities were grade 2 erythema (6.7%), grade 2 induration (4.4%), and grade 2 skin colour changes. No early IBTR was observed. Ultra-hypofractionated WBI provides favourable compliance and early clinical outcomes in EBC after BCS in a real-world setting.

Background The reproducibility of patient setup for radiotherapy is based on various methods including external markers, X-rays with planar or computerized image acquisition, and, more recently, surface matching imaging. We analyzed the setup reproducibility of 16 patients affected by prostate cancer who underwent conformal radiotherapy with curative intent by using a surface image registration system. Methods We analyzed the setup reproducibility of 16 patients affected by prostate cancer candidates for conformal radiotherapy by using a surface image registration system. At the initial setup, EPID images were compared with DRRs and a reference 3D surface image was obtained by the AlignRT system (Vision RT, London, UK). Surface images were acquired prior to every subsequent setup procedure. EPID acquisition was repeated when errors > 5 mm were reported. Results The mean random and systematic errors were 1.2 ± 2.3 mm and 0.3 ± 3.0 mm along the X axis, 0.0 ± 1.4 mm and 0.5 ± 2.0 mm along the Y axis, and 2.0 ± 1.8 mm and -0.7 ± 2.4 mm along the Z axis respectively. The positioning error detected by AlignRT along the 3 axes X, Y, and Z exceeded the value of 5 mm in 14.1%, 2.0%, and 5.1% measurements and the value of 3 mm in 36.9%, 13.6% and 27.8% measurements, respectively. Correlation factors calculated by linear regression between the errors measured by AlignRT and EPID ranged from 0.77 to 0.92 with a mean of 0.85 and SD of 0.13. The setup measurements by surface imaging are highly reproducible and correlate with the setup errors detected by EPID. Conclusion Surface image registration system appears to be a simple, fast, non-invasive, and reproducible method to analyze the set-up alignment in 3DCRT of prostate cancer patients.

This work deals with the dosimetric features of a particular phenolic compound (IRGANOX 1076 ® ) for dosimetry of clinical photon beams by using electron spin resonance (ESR) spectroscopy. After the optimization of the ESR readout parameters (namely modulation amplitude and microwave power) to maximise the signal without excessive spectrum distortions, basic dosimetric properties of laboratory-made phenolic dosimeters in pellet form, such as reproducibility, dose–response, sensitivity, linearity and dose rate dependence were investigated. The dosimeters were tested by measuring the depth dose profile of a 6 MV photon beam. A satisfactory intra-batch reproducibility of the ESR signal of the manufactured dosimeters was obtained. The ESR signal proved to increase linearly with increasing dose in the investigated dose range 1–13 Gy. The presence of an intrinsic background signal limits the minimum detectable dose to a value of approximately 0.6 Gy. Reliable and accurate assessment of the dose was achieved, independently of the dose rate. Such characteristics, together with the fact that IRGANOX 1076 ® is almost tissue-equivalent, and the stability of the ESR signal, make these dosimeters promising materials for ESR dosimetric applications in radiotherapy.

Background Image guided radiotherapy (IGRT) is an essential pre-requisite for delivering high precision radiotherapy. We compared daily variation detected by two non-ionizing imaging modalities (surface imaging and trans-abdominal ultrasound, US) to verify prostate patient setup and internal organ variations. Methods Forty patients with organ confined prostate cancer and candidates to curative radiotherapy were enrolled in this prospective study. At each treatment session, after laser alignment, all patients received imaging by a 3D-surface and a 3D-US system. The shifts along the three directions (anterior-posterior AP, cranial-caudal CC, and later-lateral LL) were measured in terms of systematic and random errors. Then, we performed statistical analysis on the differences and the possible correlations between the two modalities. Results For both IGRT modalities, surface imaging and US, 1318 acquisitions were collected. According with Shapiro Wilk test, the positioning error distributions were not Gaussian for both modalities. The differences between the systematic errors detected by the two modalities were statistically significant only in LL direction ( p  < 0.05), while the differences between the random errors were not statistically significant in any directions. The 95% confidence interval of the residual errors obtained by subtracting the random errors detected with surface images to those detected with US was included in the range from −7 mm to 7 mm corresponding to the minimum PTV margin adopted in AP direction in our clinical routine. Conclusions From our data, it emerges that setup misalignments measured by surface imaging can be predictive of US displacements after the adjustment for systematic errors. Moreover, surface imaging can detect setup errors predictive of registration errors measured by US. This data suggest that the two IGRT modalities could be considered as complementary to each other and could represent a daily “low-cost” and non-invasive IGRT modality in prostate cancer patients.

The purpose of this study was to analyze the behavior of a contouring algorithm for PET images based on adaptive thresholding depending on lesions size and target‐to‐background (TB) ratio under different conditions of image reconstruction parameters. Based on this analysis, the image reconstruction scheme able to maximize the goodness of fit of the thresholding algorithm has been selected. A phantom study employing spherical targets was designed to determine slice‐specific threshold (TS) levels which produce accurate cross‐sectional areas. A wide range of TB ratio was investigated. Multiple regression methods were used to fit the data and to construct algorithms depending both on target cross‐sectional area and TB ratio, using various reconstruction schemes employing a wide range of iteration number and amount of postfiltering Gaussian smoothing. Analysis of covariance was used to test the influence of iteration number and smoothing on threshold determination. The degree of convergence of ordered‐subset expectation maximization (OSEM) algorithms does not influence TS determination. Among these approaches, the OSEM at two iterations and eight subsets with a 6–8 mm post‐reconstruction Gaussian three‐dimensional filter provided the best fit with a coefficient of determination R2=0.90 for cross‐sectional areas ≤ 133 mm2 and R2=0.95 for cross‐sectional areas > 133 mm2. The amount of post‐reconstruction smoothing has been directly incorporated in the adaptive thresholding algorithms. The feasibility of the method was tested in two patients with lymph node FDG accumulation and in five patients using the bladder to mimic an anatomical structure of large size and uniform uptake, with satisfactory results. Slice‐specific adaptive thresholding algorithms look promising as a reproducible method for delineating PET target volumes with good accuracy. PACS numbers: 87.57.nm, 87.55.D‐, 87.57.uk

Computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally used for treatment planning of high-grade glioma. ^sup 99m^Tc-methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography (SPECT) showed high sensitivity and specificity in literature series. In the present study, it was investigated how the information provided by ^sup 99m^Tc-MIBI SPECT and MRI fusion could affect target delineation for radiotherapy of high-grade glioma. 21 patients with high-grade glioma were studied by MRI and ^sup 99m^Tc-MIBI SPECT imaging. The gross tumor volume (GTV) was outlined on MRI (MRI-GTV) and SPECT images (SPECT-GTV). Three additional volumes were analyzed: the (MRI+SPECT)-GTV representing the whole amount of MRI-GTV plus SPECT-GTV, the (MRI&SPECT)-GTV identified by the overlapping region of MRI-GTV and SPECT-GTV, and the (SPECT/MRI)-GTV identified by the extension of SPECT-GTV outside MRI-GTV. MRI contrast-enhanced and ^sup 99m^Tc-MIBI SPECT-positive lesions were found in all 21 patients. The average SPECT-GTV was slightly larger than the average MRI-GTV, with greater difference for resected than for unresected cases. The average increment of (MRI+SPECT)-GTV compared to MRI-GTV was 33%, being significantly higher for resected than for unresected cases (p = 0.006). The fusion of ^sup 99m^Tc-MIBI SPECT and MRI significantly affected the delineation of the target volume identified by MRI alone.[PUBLICATION ABSTRACT]

Computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally used for treatment planning of high-grade glioma. 99m Tc-methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography (SPECT) showed high sensitivity and specificity in literature series. In the present study, it was investigated how the information provided by 99m Tc-MIBI SPECT and MRI fusion could affect target delineation for radiotherapy of high-grade glioma. 21 patients with high-grade glioma were studied by MRI and 99m Tc-MIBI SPECT imaging. The gross tumor volume (GTV) was outlined on MRI (MRI-GTV) and SPECT images (SPECT-GTV). Three additional volumes were analyzed: the (MRI+SPECT)-GTV representing the whole amount of MRI-GTV plus SPECT-GTV, the (MRI&SPECT)-GTV identified by the overlapping region of MRI-GTV and SPECT-GTV, and the (SPECT/MRI)-GTV identified by the extension of SPECT-GTV outside MRI-GTV. MRI contrast-enhanced and 99m Tc-MIBI SPECT-positive lesions were found in all 21 patients. The average SPECT-GTV was slightly larger than the average MRI-GTV, with greater difference for resected than for unresected cases. The average increment of (MRI+SPECT)-GTV compared to MRI-GTV was 33%, being significantly higher for resected than for unresected cases (p = 0.006). The fusion of 99m Tc-MIBI SPECT and MRI significantly affected the delineation of the target volume identified by MRI alone.

Objective To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). Methods and Materials From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB), underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the biological target volume (BTV), BTVpre and BTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between BTVpre and BTVrec (BTVpre&rec) was generated and the dose coverage of BTVrec and BTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ‘‘In-Field (IF)’’, ‘‘Extending Outside the Field (EOF)’’ or ‘‘Out-of-Field (OF)’’ if D95 was respectively equal or higher than 95%, D95 was between 95% and 20% or the D95 was less than 20% of prescribed dose. Results We found 10/87 patients (11.5%) who had recurrence at primary site. Mean BTVpre was 13.1 cc (4.6-37.4 cc), while the mean BTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside BTVpre, 4 recurrences were mostly inside (61%-91%) and 4 recurrences were marginal to BTVpre (33-1%). At dosimetric analysis, six recurrences (60%) were IF, 3 (30%) EOF and one (10%) OF. The mean D99 of the overlapping volumes BTVpre&rec was 68.1Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). Conclusion Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Results support the hypothesis that an intensification of the dose on these volumes could be helpful to prevent local relapse.

This note describes a method to characterize the performances of image fusion software (Syntegra) with respect to accuracy and robustness. Computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) studies were acquired from two phantoms and 10 patients. Image registration was performed independently by two couples composed of one radiotherapist and one physicist by means of superposition of anatomic landmarks. Each couple performed jointly and saved the registration. The two solutions were averaged to obtain the gold standard registration. A new set of estimators was defined to identify translation and rotation errors in the coordinate axes, independently from point position in image field of view (FOV). Algorithms evaluated were local correlation (LC) for CT-MRI, normalized mutual information (MI) for CT-MRI, and CT-SPECT registrations. To evaluate accuracy, estimator values were compared to limiting values for the algorithms employed, both in phantoms and in patients. To evaluate robustness, different alignments between images taken from a sample patient were produced and registration errors determined. LC algorithm resulted accurate in CT-MRI registrations in phantoms, but exceeded limiting values in 3 of 10 patients. MI algorithm resulted accurate in CT-MRI and CT-SPECT registrations in phantoms; limiting values were exceeded in one case in CT-MRI and never reached in CT-SPECT registrations. Thus, the evaluation of robustness was restricted to the algorithm of MI both for CT-MRI and CT-SPECT registrations. The algorithm of MI proved to be robust: limiting values were not exceeded with translation perturbations up to 2.5 cm, rotation perturbations up to 10 degree and roto-translational perturbation up to 3 cm and 5 degree .