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Luca Nicosia,1 Claudio Vitale,1 Francesco Cuccia,1 Vanessa Figlia,1 Niccolò Giaj-Levra,1 Rosario Mazzola,1 Francesco Ricchetti,1 Michele Rigo,1 Ruggero Ruggieri,1 Stefano Cavalleri,2 Filippo Alongi1,3 1Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Verona, Negrar, Italy; 2Urology Division, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Negrar, Italy; 3University of Brescia, Brescia, ItalyCorrespondence: Luca Nicosia, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy, Tel +39 045-6014800, Fax +045-60148071, Email lucanicosia.rg@gmail.comAim: To evaluate the impact of Ialuril soft Gels® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse.Material and Methods: The data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA.Results: Grade 1– 2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT.Conclusion: Postoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results.Keywords: prostate cancer, hyaluronic acid, postoperative radiotherapy, salvage radiotherapy, hypofractionation, toxicity

BACKGROUND/OBJECTIVES: Cancer cachexia is a syndrome characterized by weight loss (WL) and sarcopenia. Aim of the study was to assess the impact of cachexia on head and neck changes during definitive cisplatin and image-guided volumetric- modulated arc radiation therapy in a series of locally advanced oropharyngeal cancer. SUBJECTS/METHODS: Volume variations of sternocleidomastoid muscle (SCM) were considered as surrogate of muscle changes related to sarcopenia. Two head and neck diameters, encompassing the cranial limits of II and III nodal levels (defined as 'head diameter' and 'neck diameter', respectively), were measured. All parameters were defined retrospectively by means of on-board cone beam computed tomography images at 1-8th to 15-22th and at last fraction (fx) of radiotherapy (RT). Cachexia was defined as WL >5% during treatment. Analysis was conducted correlating the parameter changes with three WL ranges: < 5, 5-9 and > 10%. RESULTS: Thirty patients were evaluated. One hundred and fifty contoured SCMs and three hundred diameters were collected. Median WL was 6.5% (range, 0-16%). The most significant SCM shrinkage was recorded at 15th fx (mean 1.6 cc) related to WL 5-9% and WL > 10% (P 0.001). For 'head diameter', the peak reduction was recorded at the 15th fx (mean 8 mm), statistically correlated to WL > 10% (P 0.001). The peak reduction in 'neck diameter' was registered at the 22th fx (mean 6 mm), with a gradual reduction until the end of treatment for WL >5%. CONCLUSIONS: In a homogeneous cohort of patients, present study quantified the impact of cachexia on head and neck changes. Present data could provide adaptive RT implications for further investigations. European Journal of Clinical Nutrition (2016) 70, 738-742;doi:10.1038/ejcn.2016.61; published online 13 April 2016, INTRODUCTION In definitive chemo-radiotherapy (chemo-RT) for head and neck cancer (HNC), patient weight loss (WL) has shown detrimental effects on quality of life, performance status and compliance to treatment. (1) [...]

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression., Methods: 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.)., Results: The 1-year OS was 70 %, and the median was 20.8 months (17-36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0-7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND., Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV . Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Middle meningeal artery embolization (MMAE) for the management of chronic subdural hematomas (CSDH) with ethylene vinyl alcohol (EVOH) causes an evident patient discomfort due to meningeal nociceptors stimulation. The aim of this study was to assess safety and efficacy of intra-arterial lidocaine (IAL) before MMAE of CSDH with EVOH., Methods: We analyzed all consecutive patients with bilateral CSDH undergoing MMAE with EVOH. We used a monolateral IAL injection, with casual allocation. We assessed the headache felt by patients during embolization with the visual analog scale (VAS) and compared scores obtained after embolization of both sides. We followed the STROBE guidelines for case-control studies. Paired t-test and χ 2 test were used to compare the distribution of variables in IAL vs control group., Results: Between September 2021 and March 2023, 32 patients underwent bilateral MMAE with EVOH for a CSDH. Lidocaine treatment resulted in a substantially lower VAS score compared to the control group (median 3 vs 7, p < 0.001), with no substantial side effect. Compliance also benefited from lidocaine administration., Conclusions: In patients with CSDH undergoing MMAE, IAL seems to reduce pain sensation associated with EVOH injection and to increase patients' compliance during treatment.

Background and Purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa., Materials and Methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68 Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS)., Results: a total of 150 NSBM in 95 patients were treated with 30-35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS ( p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease ( p = 0.001) and oligoprogressive patients ( p = 0.007). No grade ≥ 3 toxicity occurred., Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.

Background/aim: Sinonasal metastases arising from renal cell cancer are rare and usually managed with surgery. Few studies describe the use of radiotherapy in this specific setting, while the use of stereotactic body radiotherapy (SBRT) has been rarely reported as well., Case Report: We present the case of a solitary left sinonasal metastasis in a 65-year-old man with clear cell renal cancer who also received bilateral nephrectomy and subsequent kidney transplantation. The patient received subtotal surgery and subsequently he was candidate to SBRT to avoid systemic treatment, due to renal comorbidities., Conclusion: The patient was treated with SBRT for a total dose of 35 Gy in 5 fractions and after 24 months of follow-up there is no evidence of local relapse. No major side-effects were reported. Our experience supports SBRT as a safe and feasible treatment option in the case of sinonasal metastases from RCC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52-84). The median total dose delivered was 35 Gy (35-36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3-20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymph node oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI/LINAC n. 23748). Patients with oligometastatic lymph nodes from PCa treated with daily adaptive MR-guided SBRT on 1.5 T MR-linac were included in the study. There was a minimum required follow-up of 3 months after SBRT. The primary end-point was local progression-free survival (LPFS). The secondary end-points were: nodal progression-free survival (NPFS), progression-free survival (PFS), and toxicity. Results: A total of 118 lymph node oligometastases from PCa were treated with daily adaptive 1.5 T MR-guided SBRT in 63 oligometastatic patients. Of the patients, 63.5% were oligorecurrent and 36.5% were oligoprogressive. The two-year LPFS was 90.7%. The median NPFS was 22.3 months and the 2-year NPFS was 46.5%. Receiving hormone therapy before SBRT was correlated with a lower NPFS at the multivariate analysis (1 y NPFS 87.1% versus 42.8%; p = 0.002-HR 0.199, 95% CI 0.073-0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than was the oligoprogressive state. The median PFS was 10.3 months and the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p = 0.01-HR 0.259, 95% CI 0.117-0.574). No acute and late toxicities occurred during treatment. Conclusions: The present study is the largest prospective study of 1.5 T lymph node SBRT on MR-linac in patients with PCa. Lymph node SBRT by 1.5 T MR-linac provides high local control rates with an excellent toxicity profile.

Aim: To evaluate the impact of Ialuril soft Gels ® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse., Material and Methods: The data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA., Results: Grade 1-2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT., Conclusion: Postoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results., Competing Interests: The authors declare no conflict of interest., (© 2022 Nicosia et al.)

Background: Prostate re-irradiation is an attractive treatment option in the case of local relapse after previous radiotherapy, either in the definitive or in the post-operative setting. In this scenario, the introduction of MR-linacs may represent a helpful tool to improve the accuracy and precision of the treatment., Methods: This study reports the preliminary data of a cohort of 22 patients treated with 1.5T MR-Linacs for prostate or prostate bed re-irradiation. Toxicity was prospectively assessed and collected according to CTCAE v5.0. Survival endpoints were measured using Kaplan-Meier method., Results: From October 2019 to October 2021, 22 patients received 1.5T MR-guided stereotactic body radiotherapy for prostate or prostate-bed re-irradiation. In 12 cases SBRT was delivered to the prostate, in 10 to the prostate bed. The median time to re-RT was 72 months (range, 12-1460). SBRT was delivered concurrently with ADT in 4 cases. Acute toxicity was: for GU G1 in 11/22 and G2 in 4/22; for GI G1 in 7/22, G2 in 4/22. With a median follow-up of 8 months (3-21), late G1 and G2 GU events were respectively 11/22 and 4/22. Regarding GI toxicity, G1 were 6/22, while G2 3/22. No acute/late G≥3 GI/GU events occurred. All patients are alive. The median PSA-nadir was 0.49 ng/ml (0.08-5.26 ng/ml), for 1-year BRFS and DPFS rates of 85.9%. Twenty patients remained free from ADT with 1-year ADT-free survival rates of 91.3%., Conclusions: Our experience supports the use of MR-linacs for prostate or prostate bed re-irradiation as a feasible and safe treatment option with minimal toxicity and encouraging results in terms of clinical outcomes., 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 Cuccia, Rigo, Figlia, Giaj-Levra, Mazzola, Nicosia, Ricchetti, Trapani, De Simone, Gurrera, Naccarato, Sicignano, Ruggieri and Alongi.)

Purpose: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac., Methods and Materials: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [D p ]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the D p to at least 95% of the planning target volume (PTV), V 33.2 (PTV) ≥ 95%, a dose less than the D p to the hottest cubic centimeter (V 35 ≤ 1 cm 3 ) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V 32 ≤ 5%, V 28 ≤ 10%, and V 18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans., Results: mCycle plans improved target dose coverage, with V 33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans ( P < .001), and rectal dose sparing, with significantly reduced V 32 , V 28 , and V 18 ( P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) ( P < .001), whereas they were generally faster (-19%) in terms of optimization times ( P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) ( P  = .059) and γ (2 mm, 2%) ( P  = .432) deliverability metrics., Conclusions: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task., (© 2021 The Author(s).)

Background: Approximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated., Methods: Simulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient., Results: The agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048)., Conclusions: The dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses., (© 2021. The Author(s).)

Background: The assessment of organ motion is a crucial feature for prostate stereotactic body radiotherapy (SBRT). Rectal spacer may represent a helpful device in order to outdistance rectal wall from clinical target, but its impact on organ motion is still a matter of debate. MRI-Linac is a new frontier in radiation oncology as it allows a superior visualization of the real-time anatomy of the patient and the current highest level of adaptive radiotherapy., Methods: We present data regarding a total of 100 fractions in 20 patients who underwent MRI-guided prostate SBRT for low-to-intermediate risk prostate cancer with or without spacer. Translational and rotational shifts were computed on the pre- and post-treatment MRI acquisitions referring to the delivery position for antero-posterior, latero-lateral and cranio-caudal direction, and assessed using the Mann-Whitney U-Test., Results: All patients were treated with a five sessions schedule (35 Gy/5fx) using MRI-Linac for a median fraction treatment time of 50 min (range, 46-65). In the entire study sample, median rotational displacement was 0.1° in cranio-caudal, - 0.002° in latero-lateral and 0.01° in antero-posterior direction; median translational shift was 0.11 mm in cranio-caudal, - 0.24 mm in latero-lateral and - 0.22 mm in antero-posterior. A significant difference between spacer and no-spacer patients in terms of rotational shifts in the antero-posterior direction (p = 0.033) was observed; also for translational shifts a positive trend was detected in antero-posterior direction (p = 0.07), although with no statistical significance. We observed statistically significant differences in the pre-treatment planning phase in favor of the spacer cohort for several rectum dose constraints: rectum V32Gy < 5% (p = 0.001), V28 Gy < 10% (p = 0.001) and V18Gy < 35% (p = 0.039). Also for bladder V35 Gy < 1 cc, the use of spacer provided a dosimetric advantage compared to the no-spacer subpopulation (p = 0.04). Furthermore, PTV V33.2Gy > 95% was higher in the spacer cohort compared to the no-spacer one (p = 0.036)., Conclusion: In our experience, the application of rectal hydrogel spacer for prostate SBRT resulted in a significant impact on rotational antero-posterior shifts contributing to limit prostate intra-fraction motion. Further studies with larger sample size and longer follow-up are required to confirm this ideally favorable effect and to assess any potential impact on clinical outcomes.

Background: Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT)., Methods: The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires., Results: Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54-82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1-19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20-61); median baseline IPSS was 5 (range, 0-10). Median time for fraction was 53 min (range, 34-86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs., Conclusion: To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted., Trial Registration: Date of approval April 2019 and numbered MRI/LINAC n°23,748.

Breast cancer, gynecological malignancies and lymphomas are the most frequently diagnosed tumors in pregnant women. The feasibility of radiotherapy during pregnancy remains a subject of debate and clinicians continue to hesitate on this approach, trying to avoid radiotherapy in most cases. Since the 1990s, several technological advances, including intensity modulated and image guided radiation delivery, have been implemented in radiation oncology to improve the radiation treatment in terms of effectiveness and tolerability. It remains uncertain which short- and long-term health effects the radiation exposure of the fetus may have through advanced radiotherapy techniques. The present systematic literature review aims to summarize the limited current evidences of the feasibility and clinical results of "modern" radiotherapy procedures for the treatment of the most frequently diagnosed tumors in pregnant women., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Linac-based stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) of multiple brain lesions using volumetric modulated arc therapy (VMAT) is typically performed by a multiple-isocenter approach, i.e. one isocenter per lesion, which is time-demanding for the need of independent setup verifications of each isocenter. Here, we present our initial experience with a new dedicated mono-isocenter technique with multiple non-coplanar arcs (HyperArc™, Varian Inc.) in terms of a plan comparison with a multiple-isocenter VMAT approach., Methods: From August 2017 to October 2017, 20 patients with multiple brain metastases (mean 5, range 2-10) have been treated by HyperArc in 1-3 fractions. The prescribed doses (Dp) were 18-25 Gy in single-fraction, and 21-27 Gy in three-fractions. Planning Target Volume (PTV), defined by a 2 mm isotropic margin from each lesion, had mean dimension of 9.6 cm 3 (range 0.5-27.9 cm 3 ). Mono-isocenter HyperArc VMAT plans (HA) with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°) were generated and compared to multiple-isocenter VMAT plans (RA) with 2 coplanar 360°-arcs per isocenter. A dose normalization of 100%Dp at 98%PTV was adopted, while D 2% (PTV) < 150%D p was accepted. All plans had to respect the constraints on maximum dose to the brainstem (D 0.5cm3  < 18 Gy) as well as to the optical nerves/chiasm, eyes and lenses (D 0.5cm3  < 15 Gy). HA and RA plans were compared in terms of dose-volume metrics, by Paddick conformity (CI) and gradient (GI) index and by V 12 and mean dose to the brain-minus-PTV, and in terms of MU and overall treatment time (OTT) per fraction. OTT was measured for HA treatments, whereas for RA plans OTT was estimated by assuming 3 min. For initial patient setup plus 5 min. For each CBCT-guided setup correction per isocenter., Results: Significant variations in favour of HA plans were computed for both target dose indexes, CI (p < .01) and GI (p < .01). The lower GI in HA plans was the likely cause of the significant reduction in V 12 to the brain-minus-PTV (p = .023). Although at low doses, below 2-5 Gy, the sparing of the brain-minus-PTV was in favour of RA plans, no significant difference in terms of mean doses to the brain-minus-PTV was observed between the two groups (p = .31). Finally, both MU (p < .01) and OTT (p < .01) were significantly reduced by HyperArc plans., Conclusions: For linac-based SRS/FSRT of multiple brain lesions, HyperArc plans assured a higher CI and a lower GI than standard multiple-isocenter VMAT plans. This is consistent with the computed reduction in V 12 to the brain-minus-PTV. Finally, HyperArc treatments were completed within a typical 20 min. time slot, with a significant time reduction with respect to the expected duration of multiple-isocenters VMAT.

Background: To evaluate the feasibility and clinical preliminary results of weekly cisplatin and volumetric-modulated arc therapy to the pelvis with simultaneous integrated boost to macroscopic disease in a cohort of elderly patients., Materials and Methods: Inclusion criteria of this prospective study were age ≥70 years, Karnofsky performance status 70 to 100, locally advanced histologically proven squamous cervical carcinoma, and patients unable to undergo brachytherapy. Radiation doses prescribed were 66 Gy to the macroscopic disease and 54 Gy to the pelvic nodes in 30 fractions. Weekly cisplatin dose was 40 mg/mq., Results: A total of 30 patients were recruited. Median follow-up was 32 months (range: 8-48 months). Median age was 72 years (range: 70-84 years). The 3-year overall survival and local control were 93% and 80%, respectively. The median time to progression was 24 months (range: 6-30 months). Analyzing clinical outcome grouping based on the stage of disease, II versus III, the 3-year overall survival was 100% and 85%, respectively. The 3-year local control was 91% for stage II and 67% for stage III. Acute and late toxicities were acceptable without severe events., Conclusion: Weekly cisplatin and volumetric-modulated arc therapy-simultaneous integrated boost for radical treatment of advanced cervical cancer in the current cohort of elderly patients were feasible. Long-term results and prospective randomized trials are advocated.

Objectives: The objective of this study was to investigate fludeoxyglucose F 18 positron emission tomography/computed tomography ( 18 FDG-PET/CT) parameters as predictive of response after stereotactic ablative radiotherapy (SABR) for lung oligometastases., Methods: The inclusion criteria of the current retrospective study were as follows: (1) lung oligometastases treated by SABR, (2) presence of 18 FDG-PET/CT before and after SABR for at least two subsequent evaluations, (3) Karnofsky performance status higher than 80, and (4) life expectancy longer than 6 months. All patients were treated with a biologically equivalent dose of at least 100 Gy with an alpha/beta ratio of 10. The following metabolic parameters were semiquantitatively defined: maximum standardized uptake value (SUV max ), mean standardized uptake value (SUV mean ), metabolic tumor volume, and total lesion glycolysis., Results: A total of 50 patients met the inclusion criteria, for a total of 70 lung metastases. The pre-SABR median SUV max was 6.5 (range 4-17), the median SUV mean was 3.7 (range 2.5-6.5), and the median metabolic tumor volume was 2.3 cm 3 (0.2-31 cm 3 ). The following metabolic parameters were significantly related to complete response at 6 months: SUV max less than 5 (p < 0.001) and SUV mean less than 3.5 (p = 0.03). ΔSUV max at 3 to 6 months was +126% for lesions with in-field progression versus -26% for the remaining lesions (p = 0.002). ΔSUV mean at 3 to 6 months was +15% for lesions with in-field progression versus -26% for the remaining metastases (p = 0.008)., Conclusions: In the current analysis, complete response from lung metastasis at 6 months after stereotactic body radiation therapy was significantly associated with both the maximum and mean values of pre-SABR 18 FDG-PET/CT SUV. Longer-term trials are strongly advocated to improve the personalization of the monitoring of tumor response in patients with lung oligometastases and, consequently, monitoring of the cost-effectiveness of the health care., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Aim: To report preliminary results of a prospective study using pelvic volumetric-modulated arc therapy and simultaneous integrated boost (SIB-VMAT) on vaginal cuff postoperatively in patients with endometrial cancer (EC)., Patients and Methods: Fifty consecutive patients, submitted surgery for EC, were recruited to SIB-VMAT prescribing a dose of 54 Gy to the pelvis and 66 Gy to the vaginal cuff in 30 fractions. A 2 mm transvaginal probe and magnetic resonance imaging were used to define the vaginal cuff. Toxicity data were collected according to Common Terminology Criteria for Adverse Events v4.0; clinical outcomes were analyzed., Results: The median follow-up was 26 (range=12 to 39) months. According to International Federation of Gynecology and Obstetrics 2009, the stages were: IB1 in 20%, IB2 in 28%, IIA2 in 16%, IIB in 6%, IIIA in 2%, and IIIC in 28%. The 2-year Overall Survival and Local Control were 96% and 100%, respectively. Two pelvic node failures were registered. Acute gastrointestinal toxicity was: G0 in 12%, G1 in 52%, G2 in 36%; no case of toxicity G3 or more was observed. Acute genitourinary toxicity was: G0 in 10%, G1 in 42%, G2 in 48%; no case of toxicity G3 or more was observed. No late severe gastrointestinal or genitourinary toxicities were reported. A statistical correlation was found between acute G2 gastrointestinal toxicity with bowel V20 Gy ≥ 30%, V20 ≥ 40%, V30 ≥ 30%, Dmax ≥ 45 Gy. Acute G2 genitourinary toxicity was threefold higher with chemotherapy., Conclusion: In patients with EC, SIB-VMAT is feasible, and well tolerated. Preliminary data of clinical outcome are promising. Further prospective studies are advocated., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Lung neoplasm is the most influent cause of death for cancer. With the increasing of life expectancy in elderly patients and with the intensification of lung cancer screening by low-dose computed tomography, a further rise of the number of new non-small cell lung cancer (NSCLC) cases has been shown. Standard of care of early stage NSCLC patients is lobectomy but approximately 20% of them are not fit for surgery for comorbidities. Due to the high local control rates and the little adverse effects, stereotactic body radiation therapy (SBRT) also called stereotactic ablative radiation therapy (SABR), has rapidly replaced the conventional radiotherapy in not operable patients with stage I NSCLC. We review the evidence for use of SABR in medically inoperable patients with stage I NSCLC, and its possible extension of use to operable patients, from the perspectives of radiation oncologists and thoracic surgeons. Until the results of large randomized trials will be available, the multidisciplinary management, balancing during discussion the advantages/disadvantages of each treatment modality, could be the coming soon best approach for medically operable early-stage NSCLC. As a result, the minimally invasive thoracic surgery advantages and the SABR innovations will be translated into real clinical benefits.

Purpose: To assess the impact of mid-treatment parotid gland shrinkage on long term xerostomia during IMRT for oropharyngeal SCC., Methods and Materials: All patients treated with IMRT at a single Institution from November 2007 to June 2010 and undergoing weekly CT scans were selected. Parotid glands were contoured retrospectively on the mid treatment CT scan. For each parotid gland, the percent change relative to the planning volume was calculated and combined as weighted average. Patients were considered to be xerostomic if developed GR2+ dry mouth according to CTCAE v3.0. Predictors of the time to xerostomia resolution or downgrade to 1 were investigated at both uni- and multivariate analysis., Results: 85 patients were selected. With a median follow up of 35.8 months (range: 2.4-62.6 months), the actuarial rate of xerostomia is 26.2% (SD: 5.3%) and 15.9% (SD: 5.3%) at 2 and 3 yrs, respectively. At multivariate analysis, mid-treatment shrink along with weighted average mean parotid dose at planning and body mass index are independent predictors of the time to xerostomia resolution. Patients were pooled in 4 groups based on median values of both mid-treatment shrink (cut-off: 19.6%) and mean WA parotid pl-D (cut-off: 35.7 Gy). Patients with a higher than median parotid dose at planning and who showed poor shrinkage at mid treatment are the ones with the outcome significantly worse (3-yr rate of xerostomia ≈ 50%) than the other three subgroups (3-yr rate of xerostomia ≈ 10%)., Conclusion: For a given planned dose, patients whose parotids significantly shrink during IMRT are less likely to be long-term supplemental fluids dependent.

Unlabelled: The aim of this investigation was to evaluate the feasibility of a shortened whole-breast irradiation schedule with a concomitant boost delivered to the tumor bed once-a-week in patients with early breast cancer submitted to conservative surgery., Patients and Methods: Patients with pT1 and pT2 M0 carcinoma of the breast were selected. The basic course consisted of 4600 cGy to the whole breast in 20 fractions, 4 times a week, for 5 weeks. Once a week, a concomitant boost of 120 cGy was delivered to the lumpectomy area., Results: From March 2007 to August 2008, we assessed this radiotherapy schedule in 377 patients. According to the RTOG/EORTC Toxicity Criteria, at treatment completion, 85% of patients showed G0-1, 12% G2 and 3% G3 skin toxicity. At 24 months, late toxicity was G0 in 92%, G1 in 7% and G2 in 1%; cosmesis was excellent or good in 95% of patients. To date, at a median follow-up of 33 months, no patient has yet experienced local relapse., Conclusion: A shortened whole-breast irradiation schedule with a weekly concomitant boost may be an alternative option with acceptable toxicity and excellent cosmesis.