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Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. Advances in knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03907-w.

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.

Background Postmastectomy radiotherapy (PMRT) with TomoHelical™ (TH) or TomoDirect™ (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 To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). Materials and methods From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. Results Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23–56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. Conclusions Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

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 reported no toxicity after 6 months and good–excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Introduction: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here. Methods: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables. Results: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant (p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions. Conclusion: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals.

AIM To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. PATIENTS AND METHODS A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. RESULTS Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR

To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups.Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival.Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P.001 and P.002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa.

Objective: To report treatment times (door to door) of adjuvant treatments of breast cancer (BC) with intensity-modulated radiotherapy (IMRT). Methods: Treatment times of 62 patients with BC on the TomoTherapy Hi-Art System were collected for the analysis. Patients underwent either locoregional radiotherapy (postmastectomy radiotherapy [PMRT]) with helical modality (TomoHelical) or whole breast radiotherapy (RT) with simultaneous integrated boost (WBRT-SIB) with direct modality (TomoDirect). Door-to-door time was broken down into different steps, which were crucial to RT session. Results: A total of 594 treatment fractions were monitored. Median treatment time was 22.4 minutes (17.2–30.8) for PMRT and 14.4 minutes (10.9–23.5) for WBRT-SIB. The mean beam-on time accounted for 61.36% of the overall treatment time for PMRT compared to 57% for WBRT-SIB. The beam-on time was a much more time-consuming process. Conclusion: This treatment times analysis on the use of IMRT for BC might be useful to organize and improve the workflow efficiency in RT facilities.

To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy. Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray’s test tested difference. Kaplan–Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed. 1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2 years (9.2 years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival. Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. Advances in knowledge The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

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

To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy.Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray's test tested difference. Kaplan-Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed.1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2 years (9.2 years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival.Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

As part of the AIRC IG-13218 (NCT01913717), we analyzed data from patients with low- and intermediate-risk prostate cancer treated with extreme hypofractionated radiotherapy (RT) and simultaneous boost to the intraprostatic lesion. The aim of the study is to identify clinically meaningful information through the analysis of validated questionnaires testing gastrointestinal (GI) and genitourinary (GU) RT-related toxicity and their impact on quality of life (QoL). At the end of RT treatment, clinical assessment and prostate-specific antigen (PSA) measurements were performed every 3 months for at least 2 years and GI and GU toxicities were evaluated contextually. QoL of enrolled patients was assessed by International Prostate Symptoms score (IPSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core 30 (EORTC QLQ-C30), EORTC QLQ prostate specific (QLQ-PR25), and sexual activity by International Index of Erectile Function (IIEF-5). Patients’ score changes were calculated at the end of RT, at one month after RT and at 12 and 24 months. Sixty-five prospectively enrolled patients were analyzed. Extensive analysis of different QoL assessments showed that patients’ tolerance was satisfactory across all the considered time points, with no statistically significant change of QoL from baseline compared to that before RT. Overall survival and biochemical progression-free survival at 2-years were of 98% and 97%, respectively. Despite the toxicity of extreme hypofractionation was low and tumor control was encouraging, a longer follow-up is necessary to confirm our findings. The increasing dose to the dominant intraprostatic lesion does not worsen the RT toxicity and consequently does not affect patients’ QoL, thus questioning the possibility of an even more escalated treatment.

To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT). We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS. A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Purpose To evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed. Methods Data of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3. Results The systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9–9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5–10.5 mm in AP, 9 mm in LL and 8–10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger. Conclusions without IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.

International audience; Purpose: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy.Methods and materials: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03.Results: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3.Conclusions: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

Background Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are: Compare SBRT +/− ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL). Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses. Methods This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3 years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed: Randomized clinical study (3 years for accrual and 2 years for follow-up and data analysis); Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria; Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling. We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed. Discussion Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria. So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness. Trial registration The RADIOSA study was prospectively registered at clinicaltrials.gov (NCT03940235, May 2019).

The purpose of this study was to evaluate whether the visualization of surgical clips (SCs) on the same set of planning computed tomography (CT) of breast cancer (BC) patients influences agreement on tumour bed (TB) delineation. Planning CT (CTorig) of 47 BC patients with SCs to visualize the TB was processed in order to blur SCs and create a virtual CT (CTmod). Four radiation oncologists (ROs, 2 juniors and 2 seniors) contoured TB on both the CT sets. Centre of mass distance (CMD), percentage overlap as Dice similarity coefficient (DSC), surface distance as average Hausdorff distance (AHD) and TB volume size were analysed. The intra-observer variability when contouring TB with and without SCs was statistically significant (p-values = 0.016, 0.0002 and ≪ 0.001 for CMD, AHD and DSC, respectively). Junior ROs showed worse reproducibility compared to seniors. The median DSC was

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 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.

Introduction Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options. Methods The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome). Results The study is ongoing, and we expect to complete recruitment by the end of 2016. Conclusions Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective. Trial registration ClinicalTrials.gov identifier: NCT01913717.

OBJECTIVE: To report preliminary results of a cutting edge extreme hypofractionated treatment with concomitant boost to the dominant lesion for patients with early stage prostate cancer (PCa). METHODS: AIRC-IG-13218 is a prospective Phase II trial started in June 2015. Patients with low and intermediate risk PCa who met the inclusion criteria underwent extreme hypofractionated radiotherapy to the prostate (36.25 Gy in 5 fractions) and a simultaneous integrated boost to the dominant intraprostatic lesion (DIL) to 37.5 Gy. The DIL was identified by a multiparamentric MRI (mpMRI) co-registered with planning CT. Toxicity was assessed according to CTCAE v4.0 and RTOG/EORTC criteria. The preliminary evaluation of the first 13 patients was required to confirm the feasibility of the treatment before completing the enrollment of 65 patients. RESULTS: The first 13 patients completed the treatment between June 2015 and February 2016. With a median clinical follow-up of 17 months (range 11–26), no Grade 3 or 4 early toxicity was reported. CONCLUSIONS: Our preliminary data about early toxicity of an extreme hypofractionated schedule with concomitant boost on the DIL are encouraging. The higher number of patients expected for the trial and a longer follow-up are needed to confirm these results. ADVANCES IN KNOWLEDGE: The use of mpMRI to identify and boost the DIL is an innovative and interesting approach to PCa. Our preliminary findings suggest that dose escalation using DIL boost and extremely hypofractionated radiotherapy regimens might be a safe approach, allowing for short and effective treatment of organ-confined PCa.

Purpose. eHealth interventions may represent useful tools to deliver care and education and to meet patients’ needs within an empowerment framework. In order to design a platform for cancer patients’empowerment within the H2020 iManageCancer project, the perspective of the target population for the platform was assessed as suggested by recent studies. Men with prostate cancer often describe low levels of empowerment. The present study aims to assess the qualitative experience of prostate cancer patients during treatment in order to provide insights for clinical practice with a particular focus on the design of a web platform to promote cancer patients’ empowerment. Methods. Ten patients undergoing radiation therapy treatment took part in a semi-structured interview to explore different aspects of patient empowerment. Four main thematic areas were addressed: patient-healthcare providers’ communication, decision-making, needs and resources. A qualitative approach using thematic analysis was followed. Results. Half of the patients reported a lack in the possibility to share information and questions with healthcare providers. For decision-making, the role of healthcare providers was perceived as directive/informative, but half of the patients perceived to assume an active role in at least one interaction. Difficulties and needs included the choice of specialist or of the structure after diagnosis, clinicians’ support in self-management, surgical consequences and side effects, preparation for radiation therapy. Resources included family and social support both from a practical and from an emotional perspective, coping style, and work schedule management. Conclusions. These results suggest that relations with healthcare providers should be supported, especially immediately after diagnosis and after surgery. Support to self-management after surgery and at the beginning of radiation therapy treatment also constitutes a priority. The adoption of a personalized approach from the beginning of prostate cancer care flow may promote patient empowerment, overcoming the aforementioned needs and mobilizing resources. The social network represents an important resource that could be integrated in interventions. These considerations will be taken into account in the design of a cancer self-management platform aiming to increase patients’ empowerment.

Radiotherapy (RT) is very much a technology-driven treatment modality in the management of cancer. RT techniques have changed significantly over the past few decades, thanks to improvements in engineering and computing. We aim to highlight the recent developments in radiation oncology, focusing on the technological and biological advances. We will present state-of-the-art treatment techniques, employing photon beams, such as intensity-modulated RT, volumetric-modulated arc therapy, stereotactic body RT and adaptive RT, which make possible a highly tailored dose distribution with maximum normal tissue sparing. We will analyse all the steps involved in the treatment: imaging, delineation of the tumour and organs at risk, treatment planning and finally image-guidance for accurate tumour localisation before and during treatment delivery. Particular attention will be given to the crucial role that imaging plays throughout the entire process. In the case of adaptive RT, the precise identification of target volumes as well as the monitoring of tumour response/modification during the course of treatment is mainly based on multimodality imaging that integrates morphological, functional and metabolic information. Moreover, real-time imaging of the tumour is essential in breathing adaptive techniques to compensate for tumour motion due to respiration. Brief reference will be made to the recent spread of particle beam therapy, in particular to the use of protons, but also to the yet limited experience of using heavy particles such as carbon ions. Finally, we will analyse the latest biological advances in tumour targeting. Indeed, the effectiveness of RT has been improved not only by technological developments but also through the integration of radiobiological knowledge to produce more efficient and personalised treatment strategies.

Unfortunately, the denomination of the IEO was incorrectly published in the affiliation of this original.

OBJECTIVE: To evaluate high-precision external beam reirradiation (re-EBRT) for local relapse of prostate cancer (PCa) after radiotherapy. METHODS: This retrospective study included patients with biochemical failure and evidence of isolated local recurrence of PCa after radical/salvage EBRT or brachytherapy that received salvage stereotactic body radiation therapy (SBRT, re-EBRT). Biopsy was not mandatory if all diagnostic elements were univocal (prostate specific antigen evolution, choline-positron emission tomography or magnetic resonance imaging). Salvage SBRT (re-EBRT) was delivered with image-guided radiation therapy (RapidArc®, VERO® and CyberKnife®). RESULTS: Data of 64 patients were included, median age at salvage SBRT was 73.2 years, median pre-salvage SBRT prostate specific antigen was 3.89 ng ml(−1) . Median total dose was 30 Gy in five fractions, biologically effective dose (BED) of 150 Gy. One acute G3 genitourinary event and one late G3 genitourinary event were observed. No G ≥ 3 bowel toxicity was registered. At the median follow-up of 26.1 months, tumor progression was observed in 41 patients (64%). 18 patients (28%) experienced local relapse. 2-year local control, biochemical and clinical relapse free survival rates were 75, 40 and 53%, respectively. With BED ≥130 Gy 1-year biochemical and clinical progression-free survival rate were 85 and 90%, respectively. CONCLUSIONS: Salvage SBRT (re-EBRT) for isolated local PCa recurrence is a safe, feasible and noninvasive salvage treatment. Further investigation is warranted to define the optimal patient selection, dose and volume parameters. ADVANCES IN KNOWLEDGE: Salvage SBRT reirradiation for the locally recurrent PCa offer a satisfactory tumor control and excellent toxicity profile, if BED ≥130 Gy is administered.

Background and purpose To investigate the intra-fraction breast motion during long-lasting treatments of breast cancer with Helical Tomotherapy by means of an optical tracking system. Materials and methods A set of seven radio-transparent passive markers was placed on the thoraco-abdominal surface of twenty breast cancer patients and tracked by an infrared tracking system. A continuous non-invasive monitoring of intra-fraction motion from patient setup verification and correction to the end of radiation delivery was thus obtained. The measured displacements were analysed in terms of cyclic respiratory motion and slow baseline drift. Results The average monitoring time per patient was 15.57 min. The breathing amplitude of the chest was less than 2 mm, on average, along all anatomical directions. The baseline drift of the body led to more significant setup uncertainties than the respiratory motion. The main intra-fraction baseline drifts were in posterior and inferior directions and occurred within the first eight minutes of monitoring. Considering the intra-fraction motion only, the resultant clinical-to-planning target volume safety margins are highly patient-specific and largely anisotropic. Conclusion The non-respiratory motion occurring during prolonged treatments induces notable uncertainties. Non-invasive continuous monitoring of patient setup variations including baseline drifts is recommended in order to minimize dosimetric deviations, which might jeopardize the therapeutic ratio between target coverage and the sparing of organs at risk.