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Background: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported., Methods: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV., Results: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients., Conclusions: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off., (© 2024. The Author(s).)

Background: Possible advantages of magnetic resonance (MR)-guided radiation therapy (MRgRT) for the treatment of brain tumors include improved definition of treatment volumes and organs at risk (OARs) that could allow margin reductions, resulting in limited dose to the OARs and/or dose escalation to target volumes. Recently, hybrid systems integrating a linear accelerator and an magnetic resonance imaging (MRI) scan (MRI-linacs, MRL) have been introduced, that could potentially lead to a fully MRI-based treatment workflow., Methods: We performed a systematic review of the published literature regarding the adoption of MRL for the treatment of primary or secondary brain tumors (last update November 3, 2022), retrieving a total of 2487 records; after a selection based on title and abstracts, the full text of 74 articles was analyzed, finally resulting in the 52 papers included in this review., Results and Discussion: Several solutions have been implemented to achieve a paradigm shift from CT-based radiotherapy to MRgRT, such as the management of geometric integrity and the definition of synthetic CT models that estimate electron density. Multiple sequences have been optimized to acquire images with adequate quality with on-board MR scanner in limited times. Various sophisticated algorithms have been developed to compensate the impact of magnetic field on dose distribution and calculate daily adaptive plans in a few minutes with satisfactory dosimetric parameters for the treatment of primary brain tumors and cerebral metastases. Dosimetric studies and preliminary clinical experiences demonstrated the feasibility of treating brain lesions with MRL., Conclusions: The adoption of an MRI-only workflow is feasible and could offer several advantages for the treatment of brain tumors, including superior image quality for lesions and OARs and the possibility to adapt the treatment plan on the basis of daily MRI. The growing body of clinical data will clarify the potential benefit in terms of toxicity and response to treatment.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guerini, Noale, Mortellaro, Lisi, Bruni, Santini, Muto, Ferrera, Cossali, Morelli, PRO-EPI study group, Magrini, Spiazzi and Buglione.)

Introduction: Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure., Patients and Methods: Between 2010 and 2020, ASCC stages I-III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS ® v.26.0 software (IBM ® )., Results: A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix's Large Area High Gray Level Emphasis (GLSZM's LAHGLE), and GTV volume., Conclusions: Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM's LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonù, La Mattina, Singh, Toraci, Spiazzi, Terraneo, Barbera, Vitali, Frassine, Guerini, Triggiani, Tomasini, Morelli, Imbrescia, Andreuccetti, Frittoli, Pittiani, Grazioli, Portolani, Nicosia, Albano, Bertagna, Magrini and Buglione.)

Introduction: Actinic cheilitis (AC) is the biologic precursor of invasive squamous cell carcinoma (SCC) of the vermilion, and different treatment options have been investigated, but their efficacy is hampered by local inflammation, pain and slow recovery. Daylight photodynamic therapy (dl-PDT) has been demonstrated to represent a valuable treatment option for AC, but its feasibility is limited by weather conditions and latitude., Methods: Our study proposed to compare the efficacy and tolerability of conventional photodynamic therapy (c-PDT) and indoor daylight photodynamic therapy (idl-PDT) with a white LED lamp for the treatment of AC. Sixteen patients were enrolled in the study: 8 (50%) treated with c-PDT and 8 (50%) treated with idl-PDT. All patients completed the study protocol., Results: Both idl-PDT and c-PDT were demonstrated to be highly effective in terms of reduction of the cumulative lesional area and severity of the clinical score. Neither treatment was inferior to the other. The inflammatory reaction and the pain scores were milder with idl-PDT, whereas the cosmetic outcome was not different., Conclusion: The present findings confirm that idl-PDT can represent a valid therapeutic strategy for AC patients as well, despite the procedural difficulties and the risk of poor tolerability related to the body site., (© 2022. The Author(s).)

Aim: To evaluate the feasibility and tolerability of low-dose radiotherapy (LDRT) delivered to both lungs in the treatment of SARS-CoV-2-immune-mediated pneumonia in the COLOR-19 study (NCT0437747)., Patients and Methods: From May 2020 to April 2021 at Brescia University Radiation Oncology Department, three patients with COVID-19-related pneumonia were treated with LDRT according to the COLOR-19 protocol. All patients were treated with a single fraction at the average prescription dose of 0.7 Gy to both lungs., Results: Three patients were enrolled (two males and one female, aged 61-81 years) and underwent LDRT. Despite LDRT being safely performed without significant side-effects, two patients died (one 81-year-old male due to septic shock secondary to Escherichia coli infection and one 79-year-old male, already in poor condition, due to worsening of COVID-19). The remaining female patient (61 years old) underwent LDRT for less severe COVID-19: her clinical condition and chest X-ray improved, and she was discharged home completely asymptomatic 27 days after hospital admission. Blood levels of C-reactive protein and ferritin generally decreased after LDRT., Conclusion: Early results of the COLOR-19 study demonstrate the feasibility of LDRT for therapy of COVID-19-related pneumonia; no conclusions on the efficacy have been reached due to poor accrual., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Recently, indoor daylight photodynamic therapy (idl-PDT) has been developed; however, its efficacy and tolerability remain to be assessed., Objective: This is a not-inferiority study to compare treatment outcomes of cPDT with a red LED lamp and idlPDT with a polychromatic white LED lamp in adult patients affected by symmetrical AKs of face and/or scalp., Methods: In this comparative, intra-patient, split-face, randomized clinical trial forty-three adult patients were enrolled. Two contralateral and symmetrical target areas of the face and/or scalp harboring at least 5 AKs were selected and randomized 1:1 to treatment with cPDT and idlPDT. The AKs number and cumulative area were assessed at baseline (T0). Efficacy and cosmetic outcome were assessed 3 months after treatment (T1)., Results: Total AKs number and area reduced significantly with both idlPDT ( p  < .0001) and cPDT ( p  < .0001) in comparison to baseline. cPDT was more painful ( p  < .0001) and induced a more severe inflammation ( p  < .0001). Twenty-nine patients (70.7%) gave their overall preference to idlPDT ( p  < .001)., Conclusion: idlPDT may represent an alternative treatment protocol to cPDT for in-office treatment of AKs patients with better tolerability and a not inferior efficacy.

Background: The impact of coronavirus disease 2019 (COVID-19) has been overwhelming on patients with cancer, who may be at higher risk of developing severe disease. During the second COVID-19 outbreak in Italy, we planned universal microbiologic screening for patients scheduled for antineoplastic treatment., Methods: All patients with planned active treatment at Brescia University Radiation Oncology Department were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA with repeated nasopharyngeal swabs (NPS) from October 31, 2020. Treatment continuation, suspension, or delay was modulated for patients testing positive according to clinical presentation., Results: From October 31, 2020, to February 6, 2021, 636 patients were enrolled and 1243 NPS were performed, of which 28 (2.25%) were positive. The infection rate was 2.52%; 81.3% of the patients with a positive NPS were asymptomatic, 2 had mild disease, and 1 severe disease that led to death. All patients already on treatment with mild or asymptomatic COVID-19 carried on the therapy with no or minimal delay. Median delay for patients with infection detected before treatment start was 16.5 days., Conclusions: Detected incidence of COVID-19 was lower during the second outbreak in our patients (2.52% vs 3.23%), despite the extensive testing schedule, and substantiates the high rate of asymptomatic infections and the low mortality among patients with COVID-19 (6.3% vs 38.5% during the first outbreak). Universal SARS-CoV-2 screening for all patients with planned treatment might allow early identification of patients with COVID-19, resulting in timely management that could improve clinical outcomes and prevent spread of the infection.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

Background: immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT., Methods: we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review., Results: previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols., Conclusion: The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified., Competing Interests: Disclosure Conflicts of interest/Competing interests: none to declare, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aim: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer., Patients and Methods: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable- and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF)., Results: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate-risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate- and high-risk groups were administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate- and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively., Conclusion: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate- and high-risk localized prostate cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m 2 /q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m 2 /q1., Methods: Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules., Results: Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule., Conclusions: 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients., (© 2021. The Author(s).)

Background: Secondary malignant neoplasms (SMNs) and cardiovascular diseases induced by chemotherapy and radiotherapy represent the main cause of excess mortality for early-stage Hodgkin lymphoma patients, especially when the mediastinum is involved. Conformal radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) could allow a reduction of the dose to the organs-at-risk (OARs) and therefore limit long-term toxicity., Methods: We performed a systematic review of the current literature regarding comparisons between IMRT and conventional photon beam radiotherapy, or between different IMRT techniques, for the treatment of mediastinal lymphoma., Results and Conclusions: IMRT allows a substantial reduction of the volumes of OARs exposed to high doses, reducing the risk of long-term toxicity. This benefit is conterbalanced by the increase of volumes receiving low doses, that could potentially increase the risk of SMNs. Treatment planning should be personalized on patient and disease characteristics. Dedicated techniques such as "butterfly" VMAT often provide the best trade-off., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Psychological stress has long been recognized as a trigger for plaque psoriasis, and preliminary evidence suggests that psoriasis could be associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in impaired cortisol response to stress. This study aimed to investigate psychological stress, anxiety, depression and salivary cortisol in psoriatic patients. A cross sectional study involving 126 adult patients with plaque psoriasis and 116 adult healthy controls was conducted. Demographic, clinical data, Perceived Stress Scale (PSS) and Hospital Anxiety and Depression Scale (HADS) were collected. Cases and controls were asked whether they felt stressed in the last month, whilst psoriatic patients were also interrogated whether they found that psoriasis could have been worsened by stress. Moreover, 54 randomly selected subjects (27 psoriasis patients and 27 controls) underwent salivary cortisol testing at 8 am. PSS, HADS depression and anxiety subscales were significantly higher in psoriatic patients than in controls (17.2 ± 0.6 vs. 15.1 ± 0.8 p = 0.0289), (9.5 ± 0.3 vs. 6.2 ± 0.3 p < 0.001) and (8.2 ± 0.4 vs. 4.2 ± 0.3 p < 0.001), respectively. A higher rate of psoriatic patients reported feeling stress over the last month (45% vs. 19%, p < 0.001), and stress was considered a potential trigger for psoriasis flare-ups in 69% of cases. Psoriasis was strongly associated with higher PSS and HADS scores independently of sex, body mass index, diabetes, hypertension, dyslipidemia, and occupational status. Salivary cortisol was significantly lower in psoriatic patients compared to controls (9.6 ± 0.5 vs. 14.0 ± 1.1 nmol/L, p < 0.001). In conclusion, psoriasis was associated with higher psychological stress, anxiety and depressive symptoms, and with impaired cortisol response to stress.

Background and Purpose: Two previous "Patterns Of Practice" surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a "benchmark" Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies., Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III., Results: More than 50% of POP III patients were classified as low or intermediate risk using D'Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy., Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004-2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT-allowing for tighter margins-would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies.

In this review we summarize the currently available evidence about the role of hybrid machines for MR-guided radiotherapy for prostate stereotactic body radiotherapy. Given the novelty of this technology, to date few data are accessible, but they all report very promising results in terms of tolerability and preliminary clinical outcomes. Most of the studies highlight the favorable impact of on-board magnetic resonance imaging as a means to improve target and organs at risk identification with a consequent advantage in terms of dosimetric results, which is expected to relate to a more favorable toxicity pattern. Still, the longer treatment time per session may potentially affect the patient's compliance to the treatment, although first quality of life assessment studies have reported substantial tolerability and no major impact on quality of life. Finally, in this review we hypothesize some future scenarios of further investigation, based on the possibility to explore the superior anatomy visualization and the role of daily adapted treatments provided by hybrid MR-Linacs.

Background: Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy "red-zone"., Methods: Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed., Results: Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff., Conclusions: Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.

Background: Radiotherapy is one of the standard treatments for cutaneous lymphoma and Total Skin Electrons Beam Irradiation (TSEBI) is generally used to treat diffuse cutaneous lymphoma and some cases of localized disease. Helical IMRT (HI) allows to treat complex target with optimal dose distribution and organ at risk sparing, so helical tomotherapy has been proposed as alternative technique to TSEBI but only one preliminary report has been published., Methods: Three patients treated (from May 2013 to December 2014) with Helical IMRT, with a total dose between 24 and 30 Gy, were retrospectively evaluated. Data about dosimetric features, response and acute toxicity were registered and analyzed. Planned target coverage was compared with daily in vivo measures and dose calculation based on volumetric images used for set up evaluation as well., Results: The patients had a mean measured surface fraction dose ranging from 1.54 Gy up to 2.0 Gy. A planned target dose ranging from 85 to 120% of prescription doses was obtained. All doses to Organs At Risk were within the required constraints. Particular attention was posed on "whole bone marrow" planned V 10Gy , V 12Gy and V 20Gy values, ranging respectively between 23 and 43%, 20.1 and 38% and 9.8 and 24%. A comparison with the theoretical homologous values obtained with TSEBI has shown much lower values with TSEBI. Even if treatment was given in sequence to the skin of the upper and lower hemi-body, all the patients had anaemia, requiring blood transfusions, leukopenia and thrombocytopenia., Conclusion: Based on our limited results TSEBI should still be considered the standard method to treat total skin because of its pattern of acute and late toxicities and the dose distribution. In this particular case the better target coverage obtained with HI can be paid in terms of worse toxicity. Helical IMRT can instead be considered optimal in treating large, convex, cutaneous areas where it is difficult to use multiple electrons fields in relation with the clinical results and the limited and reversible toxicities.

Background/aim: Androgen receptor plays a key role in prostate cancer development and is a causative agent of its radio-resistance. The present study investigated the potential radio-sensitizing effect of enzalutamide, a second-generation anti-androgen, in human prostate cancer cells., Materials and Methods: The radio-sensitizing effect of enzalutamide was assessed in the androgen-dependent LNCaP cells and the androgen-independent PC3 cells by clonogenic assay and γ-H2AX assay., Results: Enzalutamide-treated LNCaP cells showed a significant decrease of cell survival at all radiation doses tested. An increased number of γ-H2AX-positive nuclei was observed, suggesting a possible impairment of the DNA repair machinery. Conversely, enzalutamide did not exhibit a significant radio-sensitizing effect on PC3 cells., Conclusion: The combination of enzalutamide with ionizing radiation significantly improves radio-sensitivity of hormone-dependent LNCaP cells. Translated in the clinical practice, our results may help to find additional strategies to improve effectiveness of radiotherapy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate biochemical relapse-free survival (bRFS), overall survival (OS), late rectal and bladder toxicities in a retrospective single institution series, also applying an in-house software for biological dose calculation., Methods: 258 patients submitted to radiotherapy after prostatectomy were considered. Differences between groups were calculated using the log-rank test and the relevant clinical and therapeutic variables were considered for multivariate analysis. PRODVH is an in-house system able to calculate mean dose-volume histograms (DVHs) of a series of patients, to convert them in biologically effective DVHs (BEDVHs) and allowing to compare them with ANOVA and t Student test., Results: Adjuvant radiotherapy (ART) and salvage radiotherapy (SRT) were performed in 131 (50.8%) and 127 patients (49.2%). At multivariate analysis advanced T stage, androgen deprivation total (ADT) and SRT resulted as independent variables related to a worst bRFS (p = 0.019, 0.001 and 0.02), while GS > 7 and SRT affected negatively OS (p 0.047 and 0.039). High grade toxicity events occurred mainly in patients treated with 3-dimensional conformal radiotherapy (3DCRT) (proctitis p = 0.006; cystitis: p = 0.041). A significantly more favorable mean rectum BEDVH for patients with G0 or G1 rectal toxicity was shown (p < 0.001). Mean BEDVH for both bladder (p < 0.01) and rectum (p < 0.05) were also significantly better for volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) plans than for 3DCRT plans., Conclusion: ART is better than SRT in terms of bRFS and OS, particularly for more aggressive cases, advanced T stage and higher Gleason Score. Postoperative prostate cancer radiotherapy should be applied as soon as possible after surgery. The use of modern techniques such as VMAT-IGRT significantly reduces toxicity.

Background: Malignant meningiomas, rare tumors that account for approximately 1%-3% of all meningioma, have high recurrence, morbidity, and mortality rate and a particularly poor outcome. Surgical excision followed by adjuvant radiotherapy is the current approach for the treatment of these tumors., Methods: In the case reported, the disease, characterized by a high proliferative index (Ki67 60%-70%), was treated with endoscopic surgery limited to the extracranial portion; then the patient underwent radiotherapy, on the residual tumor volume, to a total dose of 66 Gy delivered in 33 fractions (2 Gy/fraction) by helical intensity-modulated radiation therapy with image-guided radiotherapy daily checks (tomotherapy)., Results: Two and a half years after the treatment, the patient is alive and a partial response is maintained. The patient is healthy overall with grade I fatigue and grade II hearing loss as late toxicity (Common Terminology Criteria for Adverse Events 4.1)., Conclusions: Within a multidisciplinary approach, new radiotherapy techniques confirm their effectiveness and reliability for the treatment of malignant meningioma.

To analyse the pattern of recurrence of patients treated with Stupp protocol in relation to technique, to compare in silico plans with reduced margin (1 cm) with the original ones and to analyse toxicity. 105 patients were treated: 85 had local recurrence and 68 of them were analysed. Recurrence was considered in field, marginal and distant if >80 %, 20-80 % or <20 % of the relapse volume was included in the 95 %-isodose. In silico plans were retrospectively recalculated using the same technique, fields angles and treatment planning system of the original ones. The pattern of recurrence was in field, marginal and distant in 88, 10 and 2 % respectively and was similar in in silico plans. The margin reduction appears to spare 100 cc of healthy brain by 57 Gy-volume (p = 0.02). The target coverage was worse in standard plans (pt student < 0.001), especially if the tumour was near to organs at risk (pχ2 < 0.001). PTV coverage was better with IMRT and helical-IMRT, than conformal-3D (pAnova test = 0.038). This difference was no more significant with in silico planning. A higher incidence of asthenia and leuko-encephalopathy was observed in patients with greater percentage of healthy brain included in 57 Gy-volume. No differences in the pattern of recurrence according to margins were found. The margin reduction determines sparing of healthy brain and could possibly reduce the incidence of late toxicity. Margin reduction could allow to use less sophisticated techniques, ensuring appropriate target coverage, and the choice of more costly techniques could be reserved to selected cases.

Background: To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients., Methods: Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 "treatment plans" (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis., Results: Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the "target coverage" was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5-2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS., Conclusions: This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature's preliminary data are confirming also a radiobiological benefit for SIB. Helical IMRT-SRS seems less effective for the long time of treatment compared to other techniques.

The extent of surgery predicts overall survival (OS) in patients treated for glioblastoma (GBM). The therapeutic approach after partial resection (PR) or biopsy alone (BA) is not clearly defined. This retrospective analysis was therefore planned to analyse clinical features, treatment and survival of patients undergoing PR or BA. We analysed the clinical/therapeutic features and the outcome of 232 patients submitted to BA/PR and treated with radiotherapy (RT) with/without chemotherapy. Two subgroups (pre- and post-Temozolomide-era) were identified. The BA/PR ratio did not change with the accrual periods. In the TMZ-era, 50 % of the patients had chemotherapy; "small" volume, hypo-fractionated and "low" dose RT (<54 Gy) were delivered to 93, 38 and 44 % of the patients; corresponding values for the previous period were 4, 28, 11 and 2 % (P < 0.001). Better two-year OS was evident in the TMZ-era (18 vs 7 %); PR and chemotherapy affected OS in patients treated with hypo-fractionated, low doses RT (P = 0.02, 0.04). Limited volume, more often MRI-based, and "short" RT treatments were given mostly to unfavourably selected patients, without compromising the results of the whole group. This strategy, combined with an increased use of chemotherapy, resulted in reduced treatment burden, in an improved 2-year OS rate and prospectively in better quality of life, even in this prognostically worse subset of glioma patients.

Aims and Background: We investigated efficacy, safety, and prognostic factors of reirradiation in patients with recurrent or second primary head and neck cancer., Methods: Records of 75 consecutive patients treated with reirradiation between August 2005 and December 2013 were reviewed., Results: Median overall survival (OS) and cancer-specific survival (CSS) were 29.5 and 33.6 months. Median local control (LC) and progression-free survival (PFS) were 21.7 and 16.2 months. Univariate analysis showed that patients younger than 70 years, with a Karnofsky Performance Status (KPS) &gt;90 or with 2 or less comorbidities at time of reirradiation, have a better OS; KPS &gt;90 and biological equivalent dose (BED) &gt;72 Gy positively influenced the PFS. At multivariate analysis, KPS at reirradiation was an independent predictive factor for OS, while BED was an independent predictive factor for CSS and OS. At univariate analysis, patients with planning target volume (PTV) &gt;221 mL had worse LC and PFS rates, with results confirmed at multivariate analysis. The rate of fatal treatment-related adverse events was 6.7% (3 carotid blowout, 1 soft tissue necrosis, and 1 thromboembolic event)., Conclusions: This study confirms the role and outcomes of reirradiation. A careful selection of patients could minimize acute and late side effects and influence survival: elderly patients, with significant medical comorbidities or poor KPS, are worse candidate for reirradiation. Total dose delivered with reirradiation and PTV appear to be other potential prognostic factors. Further studies of dose escalation are needed to establish the total dose that could achieve better LC rates with a safer toxicity profile.

Aim: We retrospectively analyzed our Institution experience with these patients. The endpoints of the analysis were overall survival (OS), disease-free survival (DFS), local control (LC), metastasis free survival (MFS); results were compared with the literature., Background: Medulloblastoma in adult patients is a very rare disease; the 5 and 10-year overall survival rates range between 33-78% and 27-56%, respectively. The collection of more clinical data is strongly needed., Materials and Methods: From September 1975 to October 2006, we treated 16 adult patients (9 males and 7 females) with a histological diagnosis of medulloblastoma. Acute and late toxicities were scored according to RTOG toxicity scale. Karnofski performance status (KPS) and neurological performance status (NPS) pre- and post-RT were reported. Median age was 27 years (range 18-53 years). All the patients received cranio-spinal irradiation, two patients were also given chemotherapy. Median follow-up period was 121.5 months., Results: In January 2014, 10/16 patients were alive without evidence of disease, 6/16 died with progressive disease (1 local and spinal, 3 spinal and 2 extraneural). Ten-year LC, OS, DFS, MFS were, respectively, 84%, 67%, 60% and 59%. Univariate analysis shows that gross total resection is associated with better survival. No acute or late G3-G4 toxicity was observed., Conclusions: This experience and the analysis of the literature confirm the efficacy of postoperative RT but also the need of large datasets to better define prognostic factors and the possible role of the association of chemotherapy.

Aims and Background: To present the Italian state-of-the-art contribution to radiobiology of external beam radiotherapy, brachytherapy, and radionuclide radiotherapy., Methods and Study Design: A survey of the literature was carried out, using PubMed, by some independent researchers of the Italian group of radiobiology. Each paper was reviewed by researchers of centers not comprising its authors. The survey was limited to papers in English published over the last 20 years, written by Italian investigators or in Italian institutions, excluding review articles., Results: A total of 135 papers have been published in journals with an impact factor, with an increase in the number of published papers over time, for external beam radiotherapy rather than radionuclide radiotherapy. The quantity and quality of the papers researched constitutes a proof of the enduring interest in clinical radiobiology among Italian investigators., Conclusions: The survey could be useful to individuate expert partners for an Italian network on clinical radiobiology, addressing future collaborative investigations.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1-4N0-3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3-G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

Aims and Background: Radiotherapy is the standard treatment of glioblastoma. Three-dimensional conformal radiotherapy is the standard technique to treat glioblastoma. Intensity-modulated radiotherapy and helical intensity-modulated radiotherapy (tomotherapy) are becoming widely used. The present study compared three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy in terms of target coverage and preservation of organs at risk., Methods: Ten patients treated with three-dimensional conformal radiotherapy, with a target volume close to or superimposed to the organs at risk, were retrospectively selected. The plans were re-planned with step-and-shoot 3/5 fields intensity-modulated radiotherapy and tomotherapy. Target coverage and sparing of organs at risk were statistically compared., Results: Mean planning target volume V95% improved with sophisticated techniques (87.2%, 93.2%, 97.6% with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively). The comparison of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy did not show significant differences, whereas differences were significant when three-dimensional conformal radiotherapy and tomotherapy as well as intensity-modulated radiotherapy and tomotherapy were compared. Mean planning target volume/clinical target volume D99-D98-D95 were not different between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, but they were different between tomotherapy and three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, with better clinical target volume/and planning target volume coverage with the tomotherapy plans. Brain D33/66 were 31.1/11.8 Gy, 37.5/18.3 Gy and 28.5/14.7 Gy with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy and tomotherapy, respectively. Mean brainstem, optic nerves and chiasma Dmax were always within the defined constraints. The homogeneity index improved with intensity-modulated radiotherapy/tomotherapy compared to three-dimensional conformal radiotherapy. Tomotherapy was better than intensity-modulated radiotherapy in all patients., Conclusions: In this selected group of patients, a significant dosimetric advantage was evident for tomotherapy compared with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Significant advantages were evident in terms of panning target volume coverage (V95), D99, D98 and D95. The clinical significance of the results should be defined.

Introduction: Medulloblastoma, the most frequent brain tumor in childhood, also occurs with a wide range of characteristics in adult patients. Late relapse is common in adult medulloblastoma, and the overall survival of relapsed patients usually ranges from 12 to 15 months. Treatment at recurrence is still debated and after reoperation includes stereotactic or normofractionated radiotherapy, and high-dose chemotherapy with autologous bone marrow transplantation., Case Presentation: We report on the case of a 31-year-old Caucasian woman who underwent re-irradiation for a recurrence of medulloblastoma at nine years after first irradiation (56Gy), focusing on the radiobiological background and a review of previous studies involving re-irradiation of recurrent medulloblastoma. After surgical excision of the relapsed tumor and medical multi-agent treatment, the site of recurrence was treated using three-dimensional conformal radiotherapy to a total dose of 52.8Gy (1.2Gy/fraction/twice daily). A total biological equivalent dose of 224.6Gy (α:β = 2 Gy) was delivered to the posterior fossa (first and second treatments). No radionecrosis or local recurrence was evident at 18 months after re-irradiation., Conclusion: Re-irradiation can be considered a possible and safe treatment in selected cases of recurrent medulloblastoma in adults. The reported radiobiological considerations could be useful in other cases involving re-irradiation of brain tumors.

Purpose: Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT., Patients and Methods: We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions., Results: IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D(mean) reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V(20) reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints., Conclusion: Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 × 3 mm (up to 9 × 9 mm) does not compromise dosimetric results and allows a shorter delivery time.

Background and Purpose: To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena)., Material and Methods: Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases., Results: Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively., Conclusion: Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Dentinal sensitivity (DS) occurs frequently in adult populations in western countries. The purpose of this work was to assess the effectiveness of a new intraoral fluoride releasing device (IFRD) in reducing the level of pain in patients with primary or postsurgical dentine sensitivity., Methods: A total of 49 individuals were selected for this study, 15 of whom had post-periodontal surgery dentine sensitivity and 34 with primary sensitivity. An IFRD was applied to 39, while 10 received a placebo device. All individuals in the control group suffered from primary sensitivity. The IFRD used in this study consists of sodium fluoride encased in an acrylic polymer which releases fluoride at a rate of approximately 0.04 mg/day. All patients were asked to rinse with cold water (10 degrees C) and to indicate the level of pain on a 0 to 10 visual analog scale, 0 equalling "no pain" and 10 "maximum bearable pain." All subjects were evaluated once a week during 4 months. Statistical analysis of dentine sensitivity was performed as a univariate study, in relation to the main factors: age, gender, and primary sensitivity or postsurgical etiology., Results: Symptoms decreased dramatically in all treated patients. The level of sensitivity did not change during the first week after IFRD application, but decreased significantly within the fourth week and remained absent through the duration of the treatment (P <0.01). Difference in sensitivity with respect to different etiology was significant only after 4 weeks (P= 0.01), while there was no statistical difference with respect to age or gender., Conclusions: This paper is an initial study to evaluate the effectiveness of the IFRD. The method is fast, painless, inexpensive, and it appears to be suitable as a routine treatment. The presented data support the conclusions at this stage and warrant more comprehensive evaluation.

Patients affected with juvenile rheumatoid arthritis present clear radiological alterations of the condyles of the temporomandibular joint (TMJ) due to the inflammatory process, with a prevalence ranging from 17 percent to 63 percent. This work is a comparison between a group of subjects with juvenile rheumatoid arthritis presenting signs and symptoms of TMT dysfunction and a group of the same age not suffering from any rheumatic morbidity, but presenting an open bite > 3 mm. The aim is to verify whether the open bite can induce an alteration in mandibular function comparable to that observed in juvenile rheumatoid arthritis. Statistically significant difference is found in the juvenile rheumatoid arthritis group only regarding spontaneous and provoked muscle pain and the lateral opening deviations of the mouth, but mostly the two groups seem alike and present the same stomatognathic pattern.

Tissue hyperaemia is a physiological consequence of the temperature increase that follows, for example, the absorption of electromagnetic or ultrasound power in clinical diathermy. Diathermy, as well as other physical therapies (for example massotherapy), affects the local blood content of tissues through various mechanisms (vasoconstriction/dilatation, opening/closing of precapillary sphincters). A method for evaluating hyperaemia in superficial and medium-depth tissues has been recently proposed, which is based on four-electrode impedance measurements. A microcirculation model has also been developed to describe the hyperaemic effects of local diathermic therapy. This paper describes an electrical model of the tissues in hyperaemic conditions which allows us to correlate electrical impedance measurements to microcirculation modifications.

The four-electrode electrical impedance measurement technique is proposed for the evaluation of the hyperaemia variation in tissues treated by diathermic therapy. An impedance meter suitable for such measurements is described, and an electrical model of the heated tissues, concerning the impedance variation during diathermy and its relation with hyperaemia, is presented. The occurrence of the substantial contribution of blood to the overall transverse impedance is demonstrated by comparing the experimental results with those arising from a 2D electrical/thermal model of the treated tissues. A two-admittance model is proposed to explain the electrical behaviour of the tissues treated by diathermy. The model allows us to separate the impedance violation due to the temperature dependence of tissue conductivity from that due to the change of tissue blood content. The results of preliminary measurements of tissue impedance on healthy volunteers treated by electromagnetic diathermy are presented and discussed, showing the feasibility of impedance detection of hyperaemia variations inside tissues.

In the first weeks of pregnancy there is a significant increase of vasodilatator prostaglandins in maternal blood. This increase could be in a cause-effect relation with the increase of progesterone, BHCG and HPRL typical of the first phase of pregnancy. Blood samples of 12 normotensive women reveal that there is not a correlation between placental hormons, HPRL and the increase of prostaglandins, but these hormones seem to offer an important control on other more complex biochemical mechanisms that cause the increase of vasodilator prostaglandins.

The role of prostaglandin (PG) system in preeclampsia (pre-E) was investigated. Urinary excretion of PGE2,6-keto PGF1 alpha,2,3 dinor 6-keto PGF1 alpha, TxB2 and 2,3-dinor-TxB2 and kallikrein were determined in 10 normotensive pregnant women and 14 with pre-E. 6-keto PGF1 alpha and 2,3-dinor 6-keto PGF1 alpha (the main renal and extrarenal metabolites of vasodilator PGI2) and PGE2 excretion was lower in pre-E. TxB2 metabolites in urine were similar in the two groups of women. Our data are consistent with the hypothesis of an imbalance between vasodilator and vasoconstrictor PGs in pre-E.