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Objective: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety of combining stereotactic body radiotherapy with PARPi continuation as a strategy to treat ovarian cancer oligoprogression on PARPi. Methods: This is a multicenter retrospective study including ovarian cancer patients treated with stereotactic body radiotherapy and PARPi continuation for oligoprogression under PARPi maintenance therapy between June 2012 and May 2023 in three Italian centers. PARPi treatment was continued until further disease progression or unacceptable toxicity. The primary endpoint was the next-line systemic therapy-free interval. The Kaplan-Meier method was used to assess local control, progression-free survival, and overall survival. Univariate and multivariate Cox regression analyses were performed to evaluate potential clinical outcomes predictors. Results: 46 patients were included, with a total of 89 lesions treated over 63 radiotherapy treatments. Lymph nodes were the most frequently treated lesions (80, 89.9%), followed by visceral lesions (8, 9%) and one case with a bone lesion (1.1%). Median follow-up was 25.9 months (range 2.8-122). The median next-line systemic therapy-free interval was 12.4 months (95% CI 8.3 to 19.5). A number of prior chemotherapy lines greater than five was significantly associated with a reduced next-line systemic therapy-free interval (HR 3.21, 95% CI 1.11 to 9.32, p=0.032). At the time of analysis, 32 (69.6%) patients started a new systemic therapy regimen, while 14 (30.4%) remained on the PARPi regimen. The 2-year progression-free survival, local failure-free survival, and overall survival rates were 10.7%, 78.1%, and 76.5%, respectively. Four patients (8.7%) experienced acute toxicity with G1 gastrointestinal events. Conclusion: Stereotactic body radiotherapy combined with PARPi continuation may be

Background: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. Methods: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). Results: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. Conclusion: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Purpose: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule. Patients and Methods: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)—12 Gy in 4 fractions (3 Gy/fr) twice a day—and follow-up period ≥ 24 months. Results: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25–103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2–28.5) and 23.8% (95% CI 14.9–31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79–17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05–23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08–36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71–21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14–68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence. Conclusions: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection.

Purpose: The purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT). Methods: From July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1–T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases. Results: A total of 271 patients were included in the study. Median age was 76 (46–86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early–late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm3 was reported as predictive for moderate–severe (≥ G2) acute toxicity. Conclusions: Weekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique.

Aim: To evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women. Methods and Materials: Women aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed. Results: 481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5–6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8–83.5), BCSS 97.5 % (95 % CI, 95.5–98.6 %), OS 96.5 % (95 % CI, 94.3–97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases. Conclusions: ELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable.

Purpose: To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy. Methods: ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system. Results: Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5 years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8 years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8 years, respectively; 3, 5 and 8 years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8 years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47 days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%). Conclusions: Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological outcomes.

Aims: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients. Conclusions: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reporte

Background: Postmastectomy radiotherapy (PMRT) with TomoHelicalTM (TH) or TomoDirectTM (TD) allows a uniform target coverage. In this study, we compare treatment plans using TD and TH in the setting of hypofractionated PMRT and immediate breast reconstruction. Material and methods: The TD-treatment plans of breast cancer patients treated between May 2016 and August 2019 were retrospectively selected. All the TD plans were re-planned on TH with the same prescription dose (40.05 Gy/15 fractions) and according to our dose/volume constraints. Data about the 2 treatment plans were compared with a focus on PTV coverage and all the organs at risk (OARs) constraints. Results: Fifty patients for a total number of 100 treatment plans (50 with TD and 50 re-planned with TH) were analyzed. All the median value in the TD PTV CHEST WALL plans fulfilled the predefined planning objectives, even though TH emerged as best for target coverage with statistically significant difference for V90%. TD provided the lowest V95% for the PTV SVC, but the median value was near to the recommended value of 90% (89.8 % vs 98.6% for TD and TH, respectively). Overall, TD reached the best OARs sparing. The main statistically significant differences with TH were for contralateral breast, ipsilateral and contralateral lung. All the other dose values for TH were higher than TD, but they fulfilled the recommended/acceptable predefined planning objectives. Conclusions: In the setting of PMRT, TD compared to TH reached an acceptable target volume coverage, with an optimal sparing of OARs.

Aim: The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). Methods: Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. Results: Twenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4–114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9 Gy for bladder and D30% < 66.0 Gy, D60% < 38.0 Gy and V122.1 Gy < 5% for rectum. Conclusion: Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

Aim: To evaluate reconstruction failure (RF) rate in patients receiving implant-based immediate breast reconstruction (IBR) and hypofractionated (HF) postmastectomy radiation therapy (PMRT). Materials and methods: Stage II–III breast cancer patients, treated with HF-PMRT using intensity modulated radiotherapy were stratified in two groups according to IBR: single-stage direct-to-implant (DTI-group) and two-stage expander and implant (TE/I-group). Irradiated patients were matched with non-irradiated ones who underwent the same IBR during the same period. Prescription dose was 40.05 Gy/15 fractions to chest wall and infra/supraclavicular nodal region. Primary endpoint was RF defined as the need of major revisional surgery (MaRS) for implant removal or conversion to autologous reconstruction. Secondary endpoint was the rate of minor revisional surgeries (MiRS) including implant repositioning or substitution with another implant. Results: One hundred and seven irradiated patients (62 in TE/I-group, 45 in DTI-group) were matched with 107 non-irradiated subjects. Median follow-up was 4.2 years (0.1–6.1) In the TE/I setting, MaRS was performed in 8/62 irradiated patients (12.9%) of the irradiated TE/I group compared to 1/62 (1.6%) non-irradiated subjects (p = 0.015). In the DTI setting, MaRs occurred in 3/45 irradiated patients (6.7%) compared to 1/45 non-irradiated ones (2.2%) (p = 0.35). Overall MaRS rate was 10.3% in the irradiated group. MiRS was performed in 35.6% and 31.1% of the irradiated and non-irradiated DTI-groups (p = 0.65), respectively, and in 12.9% and 8.1% of the irradiated and non-irradiated TE/I groups (p = 0.38), respectively. Conclusions: Compared to the non-irradiated counterparts, the TE/I group showed higher rate of RF, while no statistically significant difference was observed for the DTI group. The use of hypofractionation and IMRT to implant-based IBR did not seem to increase the risk of RF which appeared to be in line with the literature.

In the last 20 years coronary computed tomography angiography (CCTA) gained a pivotal role in the evaluation of patients with suspected coronary artery disease (CAD) as finally recognized by the ESC guidelines on stable CAD. Technological advances have progressively improved the temporal resolution of CT scanners, contemporary reducing acquisition time, radiation dose and contrast volume needed for the whole heart volume acquisition, further expanding the role of cardiac CT beyond coronary anatomy evaluation. Aim of the present review is to discuss use and benefit of cardiac CT for the planning and preparation of VT ablation.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some r

Objective: Standard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy. Methods: We retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30-82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45-50.4 Gy in 25-28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external beam radiotherapy identified on MRI. The Kaplan-Meier method was used to calculate 2 years' overall survival, 2 years' progression-free survival, and 2 years' local control. Overall survival- A nd progression-free survival were calculated considering the starting of radiotherapy or neo-adjuvant chemotherapy if prescribed, while local control was calculated from the end of radiotherapy. Results: Median radiation dose to pelvis ±para-aortic lymph nodes was 50.4 Gy (45-50.4), boost treatment was homogeneously performed to a total dose of 25 Gy in five fractions every other day. After a median follow-up of 26 months (range, 4-77), tumor persistence at cervix at 6 months from the end of radiotherapy or local recurrence occurred in five women (20%), eight (32%) experienced a further distant progression (two of them had also tumor persistence). Two-year local control and overall survival rates for all stages were 78% and 67%, respectively. According to Common Termino

Background: Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define indications, prescription doses and potential adverse events of protons in this clinical scenario. Hence, the present work aims to provide a critical literature revision, and to investigate associations between fractionation schedules/ biological effective doses (BEDs), oncological outcomes and toxicities.Materials and methods: This systematic review and meta-analysis complied with the PRISMA recommendations. Inclusion criteria were: 1) curative-intent hypofractionated PBT for ES-NSCLC (>= 3 Gy(RBE)/fraction), 2) report of the clinical outcomes of interest, 3) availability of full-text written in English. The bibliographic search was performed on the NCBI Pubmed, Embase and Scopus in September 2021; no other limitations were applied. The BED was calculated for each included study (alpha/beta = 10 Gy); the median BED for all studies was used as a threshold for stratifying selected evidence into "high" and "low"-dose subgroups. Heterogeneity was tested using chi-square statistics; inconsistency was measured with the I2 index. Pooled estimate was obtained by fitting both the fixed-effect and the DerSimonian and Laird random-effect model.Results: Eight studies and 401 patients were available for the meta-analysis; median follow-up was 32.8 months. The median delivered BED was 105.6 Gy(RBE). A BED >= 105.6 Gy(RBE) consistently provided superior OS, CSS, DFS and LC rates (i.e.: 4-year OS: 0.56 [0.34-0.76] for BED < 105.6 Gy(RBE) and 0.78 [0.64-0.88] for BED >= 105.6 Gy(RBE)). The meta-analysis of proportions showed a comparable probability of developing acute grade >= 2 toxicity between the two groups, while the probability of any late grade >= 2 event was almost three-times greater for BED >= 105.6 Gy(RBE), with rib fractures being more common in the high dose group.Concl

Background: The role of radiotherapy and brachytherapy in the management of locally advanced cervical and endometrial cancer is well established. However, in some cases, intracavitary brachytherapy (ICBRT) is not recommended or cannot be carried out. We aimed to investigate whether external-beam irradiation delivered by means of intensity-modulated radiation therapy (IMRT) might replace ICBRT in gynaecological cancer when the standard ICBRT boost delivering cannot be administered for technical or clinical reasons. Materials and methods: Fifteen already delivered treatments for gynaecological cancer patients were analysed. The treatments were performed through 3-dimensional conformal radiotherapy (3D-CRT) to the whole-pelvis up to the dose of 45–50.4 Gy followed by a boost dose administered with ICBRT in high-dose-rate or pulsed-dose-rate modality. For each patient, IMRT plans were elaborated to mimic the ICBRT. We analysed the ICBRT boost versus IMRT boost in terms of dosimetric and radiobiological aspects. Results: Mean conformity index value calculated on boost volume was 0.73 for ICBRT and 0.97 for IMRT. Mean conformation number was 0.24 for ICBRT boost and 0.78 for IMRT boost. Mean normal tissue complication probability (NTCP) values for 3D-CRT plus ICBRT and for IMRT (pelvis plus boost) were, respectively, 28% and 5% for rectum; 1.5% and 0.1% for urinary bladder and 8.9% and 6.1% for bowel. Conclusions: Our findings suggest that IMRT may represent a viable alternative in delivering the boost in patients diagnosed with gynaecological cancer not amenable to ICBRT.

Purpose: To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods: Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results: Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions: Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Purpose: To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods: Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results: Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions: Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Background: The role of radiotherapy and brachytherapy in the management of locally advanced cervical and endometrial cancer is well established. However, in some cases, intracavitary brachytherapy (ICBRT) is not recommended or cannot be carried out. We aimed to investigate whether external-beam irradiation delivered by means of intensity-modulated radiation therapy (IMRT) might replace ICBRT in gynaecological cancer when the standard ICBRT boost delivering cannot be administered for technical or clinical reasons. Materials and methods: Fifteen already delivered treatments for gynaecological cancer patients were analysed. The treatments were performed through 3-dimensional conformal radiotherapy (3D-CRT) to the whole-pelvis up to the dose of 45–50.4 Gy followed by a boost dose administered with ICBRT in high-dose-rate or pulsed-dose-rate modality. For each patient, IMRT plans were elaborated to mimic the ICBRT. We analysed the ICBRT boost versus IMRT boost in terms of dosimetric and radiobiological aspects. Results: Mean conformity index value calculated on boost volume was 0.73 for ICBRT and 0.97 for IMRT. Mean conformation number was 0.24 for ICBRT boost and 0.78 for IMRT boost. Mean normal tissue complication probability (NTCP) values for 3D-CRT plus ICBRT and for IMRT (pelvis plus boost) were, respectively, 28% and 5% for rectum; 1.5% and 0.1% for urinary bladder and 8.9% and 6.1% for bowel. Conclusions: Our findings suggest that IMRT may represent a viable alternative in delivering the boost in patients diagnosed with gynaecological cancer not amenable to ICBRT.

Aims: To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT). Methods: From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1–2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable). Results: Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001). When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups. Conclusions: The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice.

Aims: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients. Conclusions: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and we

Context: The optimal management of oligometastatic prostate cancer (PCa) is still debated. Objective: The purpose of the present systematic review and meta-analysis is to collect the available evidence to date to better define the role of stereotactic body radiotherapy (SBRT) in selected patients with oligorecurrent PCa. Evidence acquisition: Study methodology complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). All prospective studies including PCa patients with nodal and/or bone oligometastases (one to five lesions) were considered eligible. Heterogeneity between study-specific estimates was tested using chi-square statistics and measured with the I2 index. A pooled estimate was obtained by fitting both fixed-effect and DerSimonian and Laird random-effect model. Evidence synthesis: Overall, six works (two randomized and the remainder observational) published between 2013 and 2020 were considered eligible. Globally, data from 445 patients were incorporated, of whom 396 were treated with SBRT (329 in observational studies and the remaining 67 in randomized ones). Regarding local progression-free survival (PFS), five studies reported values close to 100%, while one reported a value of 80% in the observation arm. The benefit in terms of biochemical PFS brought by SBRT was evident in all considered studies. Such a difference in cumulative probabilities between the intervention arm and the comparator arm is maintained even 24 mo after the baseline. All studies but one considered toxicity among the endpoints of interest. Most events were classified as either G1 or G2, and the only G ≥ 3 adverse event was reported in one trial. Conclusions: SBRT is highly cost effective, safe, and with an almost inexistent toxicity risk that makes it the perfect candidate for the optimal management of PCa oligometastatic patients. However, more solid data and a higher level of evidence are needed to affirm its role in the management of these patie

Purpose: To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. Methods: Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. Results: Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89–99) at 6 months and 92% (95% CI 83–96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. Conclusion: Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11

Rationale: to evaluate the role of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) integrated with computer tomography (CT) scan [18F]FDG-PET/CT in the staging and target volume definition in Intensity Modulated RapidarcTM Delivery (RA-IMRT) in cervical cancer. Methods: From June 2010 to December 2011, 66 patients affected by cervical cancer, candidates for definitive or adjuvant radiochemotherapy, underwent standard staging with CT and magnetic resonance imaging (MRI). All patients underwent [18F]FDG-PET/CT in order to exclude distant metastases and to define gross tumor volume (GTV). 40 and 26 patients received exclusive and adjuvant radiotherapy, respectively. RA-IMRT with simultaneous integrated boost (SIB) to the positive disease technique was employed. Results: [18F]FDG-PET/CT has changed the stage, and radiotherapy treatment planning was modified in 25% and 7.7% of patients that received definitive and adjuvant radiotherapy, respectively. Particularly [18F]FDG-PET/CT imaging showed metabolically active tumor in lymph nodes area, therefore the stage and the treatment planning changed for these patients. Conclusions: [ 18F]FDG-PET/CT leads to a better staging and definition of disease and has the potential of showing lymph-node metastasis not only within the pelvis but also in the para-aortic area. In addition, [18F]FDG-PET/CT is useful for better definition of the target volume and to produce a 'dose painted' treatment. This might also open the field for escalation dose regimens. © the authors; licensee ecancermedicalscience.

We propose a method to infer the single-particle entropy of bosonic atoms in an optical lattice and to study the local evolution of entropy, spin squeezing and entropic inequalities for entanglement detection in such systems. This method is based on experimentally feasible measurements of non-nearest-neighbour coherences. We study a specific example of dynamically controlling atom tunnelling between selected sites and show that this could potentially also improve the metrologically relevant spin squeezing.

We propose a method to infer the single-particle entropy of bosonic atoms in an optical lattice and to study the local evolution of entropy, spin squeezing and entropic inequalities for entanglement detection in such systems. This method is based on experimentally feasible measurements of non-nearest-neighbour coherences. We study a specific example of dynamically controlling atom tunnelling between selected sites and show that this could potentially also improve the metrologically relevant spin squeezing.

SUMMARY Two-surface wave decay (TSWD), i.e. the parametric excitation of electron surface waves, was recently proposed as an absorption mechanism in the interaction of ultrashort, intense laser pulses with solid targets. We present an extension of the fluid theory of TSWD to a warm plasma which treats boundary effects consistently. We also present test-particle simulations showing localized enhancement of electron acceleration by TSWD fields; this effect leads to a modulation of the current density entering into the target and may seed current filamentation instabilities.