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Giovanna Dipasquale

    Giovanna Dipasquale

    Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness... more
    Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01; soluble and aggregated forms of Aβ40, A...
    Background: Low-dose radiation therapy (LD-RT) has been shown to decrease amyloidosis or inflammation in systemic diseases and has recently been proposed as possible treatment of Alzheimer’s disease (AD). A positive effect of LD-RT on... more
    Background: Low-dose radiation therapy (LD-RT) has been shown to decrease amyloidosis or inflammation in systemic diseases and has recently been proposed as possible treatment of Alzheimer’s disease (AD). A positive effect of LD-RT on tauopathy, the other marker of AD, has also been suggested. These effects have been shown in preclinical studies, but their mechanisms are still not well understood. Objective: This study aimed to evaluate if anti-amyloid and anti-inflammatory effects of LD-RT can be observed at an early stage of the disease. Its impact on tauopathy and behavioral alterations was also investigated. Methods: The whole brain of 12-month-old 3xTg-AD mice was irradiated with 10 Gy in 5 daily fractions of 2 Gy. Mice underwent behavioral tests before and 8 weeks post treatment. Amyloid load, tauopathy, and neuroinflammation were measured using histology and/or ELISA. Results: Compared with wild-type animals, 3xTg-AD mice showed a moderate amyloid and tau pathology restricted...
    The authors have requested that this preprint be removed from Research Square.
    Background. Alzheimer’s disease (AD) is a neurodegenerative condition affecting memory performance. This pathology is characterized by intracerebral amyloid plaques and tau tangles coupled with neuroinflammation. During the last century,... more
    Background. Alzheimer’s disease (AD) is a neurodegenerative condition affecting memory performance. This pathology is characterized by intracerebral amyloid plaques and tau tangles coupled with neuroinflammation. During the last century, numerous therapeutic trials, targeting amyloid, tau or neuroinflammation, unfortunately failed. Development of new therapeutic approaches for AD is eagerly awaited. In this study, we propose to test the use of low-dose brain radiotherapy (LD-RT). LD-RT showed efficacy to reduce amyloid load in patients with peripheral pathologies and also presents anti-inflammatory effects in patients with systemic inflammatory diseases. Furthermore, previous evidence showed an effect on amyloid load, memory performance and modulation of the immune response in AD mice. Methods. The hemi-brain of 14-15 months old TgF344-AD rats was irradiated with two LD-RT schedules (5 fractions of 2 Gy, delivered weekly or daily). Rats underwent behavioral tests to assess memory an...
    Objective: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position,... more
    Objective: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. Methods: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliabil...
    To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with a sequential dose escalation hypofractionated intensity-modulated radiotherapy (IMRT) study using two... more
    To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with a sequential dose escalation hypofractionated intensity-modulated radiotherapy (IMRT) study using two different delivery methods. Since 2003, 88 and 48 patients were sequentially treated to 56 Gy and to 60 Gy (4 Gy/fraction twice weekly), respectively. IMRT with 6 MV beams was delivered with five fields in Geneva and with nine in Barcelona. Acute GI and GU side effects were scored weekly during treatment and 6 weeks after treatment completion using the Radiation Therapy Oncology Group (RTOG) toxicity scale. Clinical, technical, and dosimetric parameters were analyzed in order to assess for a potential correlation with toxicity. Grade 1–2, GU and GI toxicities during and 6 weeks after treatment completion were 64%, and 24%, and 35% and 12%, respectively. Only one Grade 4 GU toxicity, consisting of transitory urinary obstruction, was observed. Patients treate...
    Digital radiography is a field of great interest; a wide range of different imaging systems is now becoming available and it is very important to have powerful instruments to characterize and compare their imaging properties. We have... more
    Digital radiography is a field of great interest; a wide range of different imaging systems is now becoming available and it is very important to have powerful instruments to characterize and compare their imaging properties. We have evaluated imaging properties for several ...
    We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for... more
    We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for high-risk prostate cancer patients with sentinel nodes in the pararectal region. Twenty high-risk prostate cancer patients were included in a prospective trial evaluating sentinel nodes on pelvic SPECT acquisition. To be eligible for the dosimetric study, patients had to present with pararectal sentinel nodes usually not included in the clinical target volume encompassing the pelvic lymph nodes. Radiotherapy-plans including the prostate, the seminal vesicles, and the pelvic lymph nodes with the pararectal sentinel nodes were optimized for 6 eligible patients. IMXT and IMPT were delivered with 7 and 3 beams respectively and VMAT with 2 arcs. Results were assessed with Dose-Volume Histograms and predictive normal tissue complication probabilities (NTCPs) mode...
    To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Intracavitary (IC)... more
    To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.
    Purpose:In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the... more
    Purpose:In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the planning, dose calculation, and irradiation process.Methods:A thorax phantom with inhomogeneities was used, in which thermoluminescence dosimeter (TLD) and ionization chamber measurements were performed. Additionally, absolute dosimetry of the applied beams has been checked. Altogether, 30 plan‐measurement combinations have been used in the comparison study. The results have been grouped according to dose calculation algorithms, classified as “type a” or “type b,” as proposed by Knöös et al. [“Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations,” Phys. Med. Biol. 51, 5785–5807 (2006)].Results:Absolute dosimetry check under standard conditions: The mean ratio between the dose derived fro...
    Purpose The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. Methods Left-sided breast cancer patients... more
    Purpose The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. Methods Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional poly...
    Aim: To test 3D-printed immobilization devices for future use in magnetic resonance-guided focused ultrasound hyperthermia. Material & methods: Using a surface scanner, patient-specific pelvic immobilization devices were 3D printed. The... more
    Aim: To test 3D-printed immobilization devices for future use in magnetic resonance-guided focused ultrasound hyperthermia. Material & methods: Using a surface scanner, patient-specific pelvic immobilization devices were 3D printed. The setup reproducibility was measured both on linear accelerator (LINAC) and magnetic resonance. An ultrasound imaging probe was used to acquire reference images and later to acquire images once attached into the embedded holder. Results: Prepositioning accuracy was tested at LINAC using an optical surface monitoring and MRI and showed submillimeter accuracy and small angular rotations. Agreement was high between the ultrasound reference images versus the immobilized probe. Conclusion: Reported results are considered as a promising step toward a fast and precise positioning of patients and an easier integration of radiotherapy and magnetic resonance-guided focused ultrasound hyperthermia.
    Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right... more
    Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010–2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant ...
    PURPOSE Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a... more
    PURPOSE Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a decreased quality or increased complexity of the treatment plan. The aim of this study is to investigate the necessity of using avoidance sectors (AvSe) using a 2-arcs coplanar pelvic volumetric modulated arc-therapy (VMAT) planning. METHODS We evaluated: (1) The dose calculation error of a static 6MV open beam traversing a MHI; (2) The magnitude of an error's decrease within the planning target volume (PTV) for a 360° VMAT treatment without AvSe as compared to the static open beam; (3) The dosimetric influence of MHI misalignment generated by patient's repositioning rolls during image-guided radiotherapy (IGRT). RESULTS (1) In the static 6MV beam configuration, for distances between 0.5cm and 6cm from the MHI, the median (maximum, number of points) dose calculation error was -1.55% (-2.5%, 11); (2) Compared to the static open beam, in the 360° VMAT treatment without AvSe a simulated error was decreased by a factor of 4.4/2.4 (median/minimum); (3) MHI anterior-posterior misalignment exceeding 0.6cm, resulted in error at PTV surface of >2%. CONCLUSIONS A standard 2 coplanar arcs 360° VMAT treatment, with dedicated artifact reduction algorithms applied, decreased the error of static beam traversing MHI, in patients presenting a bilateral MHI and might be used to treat the pelvic region without MHI avoidance.
    Background: A 2-level factorial pilot study was conducted in 2007 just before starting a randomized clinical trial comparing tomotherapy and conventional radiotherapy (CR) to reduce cardiac and pulmonary adverse effects in breast cancer,... more
    Background: A 2-level factorial pilot study was conducted in 2007 just before starting a randomized clinical trial comparing tomotherapy and conventional radiotherapy (CR) to reduce cardiac and pulmonary adverse effects in breast cancer, considering tumor laterality (left/right), target volume (with/without nodal irradiation), surgery (tumorectomy/mastectomy), and patient position (prone/supine). The study was revisited using a penalty score based on the recently developed mean absolute dose deviation (MADD). Methods: Eight patients with a unique combination of laterality, nodal coverage, and surgery underwent dual tomotherapy and CR treatment planning in both prone and supine positions, providing 32 distinct combinations. The penalty score was applied using the weighted sum of the MADDs. The Lenth method for unreplicated 2-level factorial design was used in the analysis. Results: The Lenth analysis identified nodal irradiation as the active main effect penalizing the dosimetry by 1...
    INTRODUCTION To prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage... more
    INTRODUCTION To prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI. MATERIAL & METHODS The system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively. RESULTS The median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20seconds against 214seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p<0.01). CONCLUSIONS Compared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.
    This study evaluates edited/reviewed automatically-segmented structures of the breast target in patients planned in prone position and their dose/volume effects. Contouring times were reduced using automatic-segmentation.... more
    This study evaluates edited/reviewed automatically-segmented structures of the breast target in patients planned in prone position and their dose/volume effects. Contouring times were reduced using automatic-segmentation. Similarity-indexes and pendulousness showed that targets with Dice values over 0.965 and high pendulousness, presented the best dosimetric results.
    To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). Between 2003 and 2006, 82 prostate cancer patients with a... more
    To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk ≤20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). All patients completed the treatment without interruptions. No patient presented with Grade ≥3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2% ± 2.9% and 96.1% ± 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% ± 5.9%, 76.4% ± 8.8%, and 77.5% ± 8.9% for low-, intermediate-, and high-risk groups, respectively. In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.
    A comparative treatment planning study was performed to compare volumetric-modulated arc (RA) to conventional intensity modulated (IMRT) for involved-field (IFRT) and involved-node (INRT) radiotherapy for Hodgkin lymphoma (HL). Plans for... more
    A comparative treatment planning study was performed to compare volumetric-modulated arc (RA) to conventional intensity modulated (IMRT) for involved-field (IFRT) and involved-node (INRT) radiotherapy for Hodgkin lymphoma (HL). Plans for 10 early-stage HL female patients were computed for RA and IMRT. First, the planning target volume (PTV) coverage and organs at risk (OAR) dose deposition was assessed between the two modalities. Second, the OAR (lung, breast, heart, thyroid, and submandibular gland) dose-volume histograms were computed and compared for IFRT and INRT, respectively. For IFRT and INRT, PTV coverage was equally homogeneous with both RA and IMRT. By and large, the OAR irradiation with IFRT planning was not significantly different between RA and IMRT. For INRT, doses computed for RA were, however, usually lower than those with IMRT, particularly so for the lung, breast, and thyroid. Regardless of RA and IMRT modalities, a significant 20-50% decrease of the OAR computed mean doses was observed with INRT when compared with IFRT (Breast D(Mean) 1.5 +/- 1.1 vs. 2.6 +/- 1.7 Gy, p < 0.01 and 1.6 +/- 1.1 vs. 2.9 +/- 1.9 Gy, p < 0.01 for RA and IMRT, respectively). RA and IMRT results in similar level of dose homogeneity. With INRT but not IFRT planning, the computed doses to the PTV and OAR were usually higher and lower with RA when compared to IMRT. Regardless of the treatment modality, INRT when compared with IFRT planning led to a significant decrease in OAR doses, particularly so for the breast and heart.
    To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic... more
    To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

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