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• CDK4/6 inhibitors represent the standard-of-care for metastatic HR+/HER2 breast cancer. • Available data on CDK4/6 inhibitors and concomitant RT are conflicting. • We showed that concurrent RT did not increase treatments severe toxicity. • A consensus guideline to help physician's routine practice is strongly needed. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting. From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate. We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3–78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55). Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). Methods and materials: A total of 2093 patients were treated between 2000 and 2008. 10Gy boost was prescribed in case of FMS>5mm; 16Gy boost with FMS between 2 and 5mm; 20Gy boost in case of FMS<2mm or positive. Results: After a median follow up of 5.2years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p =0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2–5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p =0.045), triple negative subtype (p =0.036) and higher T-stage (p =0.02) resulted as the independent predictors of LR occurrence. Conclusions: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. Methods: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30–80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan–Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. Results: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19–1.95), pT status (HR 1.62, CI 1.31–2.01), positive axillary lymph nodes (HR 1.92, CI 1.66–2.22), and local recurrence (HR 4.58; CI 3.66–5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p =0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35–0.63), use of tamoxifen (HR 0.42; CI 0.25–0.71), surgical margins (HR 2.00; CI 1.21–3.30), and chemotherapy (HR 0.53; CI 0.31–0.91) emerged by multivariate analyses as significant breast relapse predictors. Conclusion: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival. [Copyright &y& Elsevier]

The rising incidence of Human Papilloma Virus (HPV) related oropharyngeal squamous cell carcinoma (OPC) in the older population has been confirmed by recent epidemiologic reports. An increase of over 50% is expected in the population aged older than 65 years in the next decade. Some authors have focused their investigations on the "late" elderly subgroup defined as patients (pts) aged 75 years or older, still underrepresented in clinical trials. Indeed, there is a significant lack of data on their disease trajectory. The purpose of our experience was to evaluate the pattern of clinical practice in this specific subgroup of pts within the Italian Association of Radiotherapy and Clinical Oncology (AIRO). [Display omitted] An observational retrospective study was conducted over a 6-year period (2015-2021). Consecutive patients older than 75 years at diagnosis with a histologically-confirmed HPV positive (p16 immunohistochemistry/HPV DNA-in situ hybridization) OPC eligible for a curatively-intended treatment were included. Overall survival (OS) was defined as the time from OPC diagnosis to last follow-up or death from any cause. Progression-free survival (PFS) was defined as the time from the last day of curative-intended treatment to disease progression or death from any cause. Median OS and PFS was estimated by the Kaplan-Meyer method. A log-rank test was employed to test different variables: smoking history, presence of caregiver, employed treatment modality and age (< or > 80 years) correlated with longer OS. Hazard ratios (HR) for the association between the variables of interest and the risk of death were obtained by univariate Cox regression analysis. A p-value <0.05 was considered statistically significant. Acute toxicity was evaluated according to CTCAE v. 5.0 [Display omitted] A cohort of 95 pts was included in our analysis. The median age was 78 years (table 1). ECOG PS 0-1 and locally advanced disease were reported for the vast majority of patients, 92.6% and 89.4% (in stage III/IV according to TNM 7thedition) respectively. As expected, exclusive radiotherapy (RT) was the most common adopted strategy. After a median follow- up of 25 months (range: 0-116), 64 patients were alive (67.3%). The one and two-year PFS were 75% and 67%, the median PFS was not reached (Figure 1a). The one and two-year OS rates were 83% and 75%, respectively, whereas the median OS was not reached. Among the tested variables, belonging to the group of age >80 years was associated with a worse OS (p=0.0429; HR for death, 2.15, 95% CI 1.00-4.60, Figure 1b), whereas no impact on survival was associated to the smoking history (p=.011), treatment modality (p=0.32) and presence of caregiver (p=0.65). The toxicity profile was acceptable (>G3 toxicity of 29.4%), although 6 patients (6.3%) died due to potential treatment-related complications. Further analyses on radiation dose, target volumes and pattern of failure will be reported To the best of our knowledge, our series represents one of the largest to date on "late" elderly population with non-metastatic HPV positive OPC treated with a curatively-intended, RT-based approach. Thanks to the appropriate selection of pts, an optimal survival outcome can be achieved with standard treatment options, in line with data reported for the younger population. Further prospective studies investigating larger series of older pts are warranted in order to confirm our conclusions. [ABSTRACT FROM AUTHOR]

After KEYNOTE 048, PDL1 CPS score has become essential in treatment choice for patients with squamous cell carcinoma of the head and neck (HNSCC) not eligible for curative treatment. This report aims to analyze efficacy and safety outcomes in a cohort of patients treated in our center with first line systemic therapy (FLST) from 2021. We collected retrospectively data about stadiation and treatment from patients with recurrent/metastatic HNSCC treated in our center with FLST according to CPS. The primary endpoints were overall survival (OS) and progression-free survival (PFS) (considered from the start of FLST). Toxicity data were reported according to CTCAEv4.0. [Display omitted] Thirty-nine patients who underwent FLST in our center between Jan 2021 and May 2023 were included in this retrospective study, with a median follow-up of 9 months [95%CI 1.2-16.8]. Median age was 63 years and PS ECOG mostly 0-1 (90%); CPS resulted negative in 8 (21%), >1 in 9 (23%) and >20 in 22 (56%) patients. 16 patients (41%) had distant metastases, the others locoregional disease not eligible for radical treatment. EXTREME schedule was chosen in the 8 CPS-negative patients; 20 of the CPS-positive cohort received Platinum+5FU+Pembrolizumab (PFP) and 11 Pembrolizumab alone. Considering all patients, median OS was 9 months [95%CI 3.1-14.8], 1-year OS 46%, 2-year OS 20%; median PFS was 5 months [95%CI 3.4-6.5] (Figure 1). One-year PFS 21%. Pembrolizumab group had a median OS of 9 months [95%CI 3.5-14.5] and 1-year OS of 38%; PFP group had median OS of 10 months [95%CI 0-23.9], 1-year OS 45% and 2-year OS 30%. At univariate analysis, younger age was associated with longer survival with a median OS of 17 months [95%CI 4.2-29.7] and 5 months [95%CI 1.7-8.3] for patients aged <70y and >70y respectively (p=0.01). Regarding toxicity, we reported 15 events > G3; the most frequent were mucositis (4) and neutropenia (4) in chemotherapy groups; only 3 occurred with Pembrolizumab alone. In our cohort, patients with recurrent/metastatic HNSCC had efficacy and safety outcomes in line with published chemo-immunotherapy data (KN048). Younger age was significantly associated with longer survival. [ABSTRACT FROM AUTHOR]

Loco-regional recurrence (LRR) is the predominant pattern of failure in locally-advanced head and neck cancer (HNC), both in squamous cell carcinoma (SCC) and non-squamous histotypes. Despite the proven role of radiotherapy (RT) as primary treatment strategy, there is sparse evidence on the use of reirradiation (ReRT) in recurrent HNC (rHNC). Various regimens of hypofractionation have been described in the literature, without a clear consensus. The aim of our single-centre study is to evaluate the clinical outcome of unresectable rHNC patients treated with Cyberknife-based (CK) hypofractionated reRT. We retrospectively analyzed data from consecutive patients with rHNC who received CK reRT at our institution. All eligible patients had a recurrent, non-metastatic, previously irradiated unresectable HNC. Each case was discussed at a multidisciplinary level before treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and log rank test with time measured from the date of last day of reRT to date of local recurrence, progression of disease or death, respectively. [Display omitted] First curatively intended course of RT was delivered from 1997 to 2020, concomitantly with chemotherapy or not. Thirty-five patients received Cyberknife (CK)-based hypofractionated reRT. The majority of patients (22, 63%) had a diagnosis of SCC and 13 patients (37%) had other histotypes than SCC. The median age of the cohort was 62 years at diagnosis. The CK reRT was performed from 2012 to 2022. The most commonly adopted schedules of reRT were 25Gy (57%) and 30Gy (43%) in 5 fractions on alternating days. After a median follow-up of 12 months (range 2-48), 6 out of 35 patients were alive. Causes of death were related to HNC in 12 patients and in 9 to other causes. The median LC and the 1-year LC rate were 10 months (95% CI 6,6-13,4 months) and 42%, respectively. The median PFS and OS and the 1-year PFS and OS rates were 8 months (95% CI 6.1-9,8 months), 18 months (95% CI 11,8-24,1 months) and 15% and 71% (Figure 1), respectively. At univariate analysis, a negative correlation between time to CK reRT < 12 months and LC (p 0.01) was reported. Moreover, a positive trend association between time from first to second irradiation ≥ 12 months and OS (p 0.09) was shown, in line with findings available from the literature. A significantly better OS was found in patients aged < 65 years (p 0.045). From our analysis, hypofractionated ReRT can be viewed as a well-tolerated treatment option for rHNC with potential for prolonged local control in appropriately selected patients. [ABSTRACT FROM AUTHOR]

• Novel treatments are needed for high-risk locally advanced head and neck cancer. • Combining Durvalumab with Cetuximab and radiotherapy had preliminary efficacy. • Albeit limited, our findings warrant further investigations in PD-L1 positive cases. To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma. At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021. Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7–16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4). Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations. [ABSTRACT FROM AUTHOR]

• The administration of T-DM1 within 1 year of brain stereotactic radiosurgery (SRS) was associated with an elevated risk of both overall and symptomatic radionecrosis in per-patient analysis. • Analysis by per-treatment has identified an increase in overall and symptomatic radionecrosis associated with the use of T-DM1 within 1 year of SRS. • There was an increase in radionecrosis even in patients who received SRS and T-DM1 within 1 year, not just with concurrent use. • Previous whole brain radiotherapy substantially increased the risk of radionecrosis when T-DM1 was used within 1 year of SRS. To investigate the potential relationship between trastuzumab emtansine (T-DM1) treatment and radionecrosis induced by brain stereotactic radiosurgery (SRS) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Patients with HER2-positive breast cancer who were diagnosed with brain metastasis and received both SRS and HER2-targeted agents between 2012 and 2022 were retrospectively analyzed. Patients who received T-DM1 within 1 year (either before or after) of SRS were considered as 'T-DM1 exposure (+)'. T-DM1 exposure (−) group had other HER2-targeted agents or received T-DM1 more than 1 year before or after SRS. Symptomatic radionecrosis was defined as Common Terminology Criteria for Adverse Events grade 2 or greater. A total of 103 patients with 535 treatment sessions were included from seven tertiary medical centers in Korea and Italy. The median follow-up duration was 15.5 months (range 1.1–101.9). By per-patient analysis, T-DM1 exposure (+) group had an increased risk of overall radionecrosis after multivariate analysis (HR 2.71, p = 0.020). Additionally, T-DM1 exposure (+) group was associated with a higher risk of symptomatic radionecrosis compared to T-DM1 exposure (−) patients (HR 4.34, p = 0.030). In per-treatment analysis, T-DM1 exposure (+) was linked to higher incidences of overall (HR 3.13, p = 0.036) and symptomatic radionecrosis (HR 10.4, p = 0.013) after multivariate analysis. A higher prevalence of radionecrosis was observed with T-DM1 exposure (+) and a previous history of whole brain radiotherapy. An increased risk of radionecrosis was observed in patients receiving T-DM1 with brain SRS. Further research is needed to better understand the optimal sequence and interval for administering T-DM1 and SRS. [ABSTRACT FROM AUTHOR]

• Re-irradiation (re-RT) of intracranial recurrent meningiomas is still matter of debate and limited by radiation tolerance of the surrounding tissue and the increased risk of side effects. • Re-RT is increasingly considered in current clinical practice, but its efficacy and safety for brain tumors are still under investigation. The optimal choice of patient selection, RT modalities and dose for re-irradiation are not well established yet. • This retrospective analysis aims at providing data about clinical outcomes, toxicities and prognostic factors in a cohort of 181 intracranial recurrent meningioma patients treated in 8 different Italian centers with different RT modalities. Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan–Meier curves and Cox regression models were used for analysis. Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20–89) and median Karnofsky Performance Status (KPS) was 90 (range 60–100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7–6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19–0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21–0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27–0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48–5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80–5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21–0.64, p < 0.001; HR 0.38, 95 % CI 0.20–0.72, p = 0.003 and HR 0.31 95 % CI 0.13–0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice. [ABSTRACT FROM AUTHOR]

• Optimal dose and fractionation in SBRT for oligometastatic cancer patients remain unknown. • In the first 1,099 OligoCare patients, median number of fractions was 5 and fraction dose 9.7 Gy. • On multivariate analysis, dose varied significantly for primary cancer type and metastatic sites. • Future analysis will address safety and efficacy of this site- and disease-adapted SBRT practice. Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/β of 10 Gy for all primaries, and cancer-specific α/β of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3–5) and median dose per fraction was 9.7 (IQR, 7.7–12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503). [ABSTRACT FROM AUTHOR]

In this perspective paper, the findings of the recently published LUMINA study are critically evaluated, with an emphasis on the need for careful interpretation and a thoughtful approach in clinical practice. The LUMINA trial, which investigates the role of adjuvant endocrine therapy in low-risk breast cancer patients, is assessed for its limitations, including a highly selective patient cohort and an insufficient follow-up period. The importance of long-term data and further trials to inform clinical decisions effectively is emphasized. While the LUMINA study does not support an immediate change in practice, it is seen as a foundation for generating hypotheses to guide ongoing clinical trials. This important study has served as inspiration to develop this perspective paper, which takes into account ongoing studies and the toxicity profile of postoperative treatments in low-risk recurrence breast cancer. The need for a patient-cantered approach is stressed, considering individual wishes and desires in decision-making, despite the complexity of articulating these aspects in guidelines. A wise interpretation of available findings is essential to ensure sound clinical decision-making before broadly applying omission of radiation therapy. [ABSTRACT FROM AUTHOR]

• Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. • No direct comparison between ICUD/ONB and TMT is available. • These data should be used in clinical practice to empower patients in deciding about local treatment choice. Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patients treated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference −0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference −0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios. [ABSTRACT FROM AUTHOR]

External beam partial breast irradiation (PBI) provides equal oncological outcomes compared to whole breast irradiation when applied to patients with low risk tumours. Recently, linacs with an integrated magnetic resonance image-guidance system have become clinically available. Here we report the first-in-human PBI performed at the 1.5 T MR-Linac, with a focus on clinical feasibility and investigation of the air electron stream effect (ESE) and the electron return effect (ERE) in the presence of the 1.5 T magnetic field, which might influence the dose on the chin (out-of-field dose, due to the ESE), the skin and the lung/chest wall interface (in-field dose, ERE). A 59 years old patient affected by a 15 mm unifocal grade 1 carcinoma not special type of the right breast staged pT1c pN0 cM0 was planned and treated at Unity 1.5 T MR-Linac. To investigate the ERE and the ESE, an MR-Linac treatment plan was simulated without considering the 1.5 T B field using a research version of Monaco (V. 5.19.03). In vivo dosimetry was performed using Gafchromic® EBT3 films placed on top and underneath a 1 cm bolus which was placed on the patient's chin. The plans with and without 1.5 T magnetic field were compared in terms of dose to the chin, to the skin and to the interface lung/chest wall. Finally, the dose on the chin measured with the in vivo dosimetry was compared with the dose calculated by Monaco. PBI using the 1.5 T MR-Linac was successfully performed with a 7 MV photon 7-beams IMRT step-and-shoot plan. The treatment was well tolerated, the patient developed a slight acute toxicity, i.e. breast skin erythema and breast oedema CTC V.4 grade 1. The plan with 1.5 T magnetic field documented a fractional dose of 0.17 Gy in the chin area (2.6 Gy in 15 fractions), which was reduced to 0.05 Gy (0.75 in 15 fractions) by the presence of 1 cm bolus. The simulated plan without magnetic field showed a dose reduced by 2.3 Gy in the chin area. With the in vivo dosimetry a fractional dose of, respectively, 0.12 Gy and 0.034 Gy on top and underneath the bolus were measured (1.8 and 0.51 Gy in 15 fractions). The plan with 1.5 T magnetic field showed a skin D 2 of 40 Gy and a skin V 35 of 40.2%, which were reduced to, respectively, 39.7 Gy and 24.9% in the simulation without magnetic field. At the interface lung/chest there were no differences in DVH statistics. PBI with the 1.5 T MR-Linac was performed for the first time. ESE is accurately calculated by the treatment planning system, can be effectively reduced with a 1 cm bolus and is comparable to dose of cone beam-CT based position verification. The additional dose caused by ERE is not associated with an increased risk of acute toxicity. [ABSTRACT FROM AUTHOR]

Highlights • A robust treatment technique was established for APBI VMAT with Pinnacle3 Auto-Planning. • The technique was validated on a set of 20 left-sided APBI patients by comparison with manual plans. • PTV coverage and dose homogeneity were improved in AP plans compared to manual. • A reduction in ipsilateral breast V 15 Gy and ipsilateral lung V 10 Gy was observed when compared to manual Pinnacle. • AP for VMAT APBI was proven to be at least equivalent and overall superior to manual planning. Abstract Purpose To evaluate the quality of accelerated partial breast irradiation (APBI) plans generated by the Auto-Planning module of a commercial treatment planning system (TPS). Material and methods Twenty patients, previously planned and treated with manual planning in a TPS (manM), were re-planned using manual (manP) and automatic (AP) module of a different TPS. Plans were compared in terms of dosimetric parameters, degree of modulation, monitor units and treatment time, and by blind qualitative scoring by a physician. Dosimetric verification was evaluated in terms of γ passing rate and point dose measurements. Statistical differences were evaluated using paired two-sided Wilcoxon's signed-rank test. Results A statistically significant improvement in PTV coverage was observed for AP plans compared to clinical plans, while no differences in organs at risk doses were observed. When compared to manP plans, a statistically significant improvement was observed for PTV coverage and homogeneity and for the ipsilateral breast and lung dosimetric parameters. The modulation degree was reduced with AP compared to manM treatment plans, while it was increased compared to manP treatment plans. No differences were observed in γ passing rate. Planning time was reduced from (54.5 ± 8.0) min for manM planning and (62.8 ± 15.0) min for manP planning to (9.8 ± 1.1) min for AP. In the qualitative scoring, AP plans were considered superior both to manM (10/20 cases) and manP plans (12/20 cases) with high clinical relevance. Conclusion Automatic planning for VMAT APBI was always at least equivalent and overall superior to manual planning. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose Breast-conserving surgery (BCS) and whole breast radiation (RT) with or without endocrine therapy (ET) represent the standard of care for ductal carcinoma in situ (DCIS). The use of adjuvant treatments after surgery is still controversial in this setting. We performed a retrospective multicenter analysis on a series of DCIS patients treated with BCS and adjuvant RT. Materials and methods We collected clinical data from nine Italian centers on 1072 women having a diagnosis of DCIS and treated between 1997 and 2012. We reported on the 5- and 10-year local recurrence (LR) rates, overall survival, and breast cancer specific survival (BCSS) employing the Kaplan–Meier method. Results At a median follow-up of 8.4 years, 67 LR (6.3%) and 47 deaths (4.4%) were observed. LR rates at 5 and 10 years were 3.4% and 7.6%, respectively. BCSS rates at 5 and 10 years were 99.7% and 99.1%, respectively. At univariate regression analysis, postmenopausal state (p = 0.009), estrogen receptor (ER) (p = 0.0001) and progesterone receptor (p = 0.018) positivity and ET (p = 0.006) were inversely correlated with LR. Final surgical margins (FSM) status <1 mm was significantly correlated with higher LR (p = 0.003). At multivariate regression analysis postmenopausal state (p = 0.03), and ER positive (p = 0.045) maintained the significant favorable feature, while FSM <1 mm (p = 0.024) confirmed its negative impact on LR. Conclusions Our real-life study pointed out the significant favorable prognostic role of postmenopausal state and ER positive status on LR occurrence. FSM <1 mm was significantly correlated to a higher chance to experience LR. [ABSTRACT FROM AUTHOR]

Purpose Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Methods Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. Results A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. Conclusions This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G. Materials and methods: Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED). Results: Development of grade ⩾2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ⩾2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03). Conclusions: Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients. [Copyright &y& Elsevier]

Abstract: Background and purpose: Radiation proctitis is a side effect which can occur after pelvic radiation therapy. Currently available questionnaires do not comprehensively assess the range of problems, nor impact on quality of life associated with proctitis. This article reports on the cultural testing phase of an EORTC module (QLQ-PRT21) developed to assess radiation proctitis specific issues and designed to be used in conjunction with the EORTC core quality of life questionnaire (QLQ-C30). Methods: The previously developed 21-item module, pre-tested in Australia, was translated into Norwegian, German, French and Italian. Patients completed the EORTC QLQ-C30 and module questionnaires towards the end of their radical pelvic radiation treatment to target acute side effects. Patients experiencing chronic proctitis were also surveyed. Patients also participated in structured interviews to determine issues of comprehensibility, coverage and relevance. Results were compared with Australian data. Results: Questionnaires were completed by 64 European patients. The module was found to be relevant and culturally acceptable to participants. Feedback has led to minor translation modifications and the inclusion of two additional questions. Conclusion: This module is ready for Phase IV testing which will consist of large scale field testing with the aim to perform psychometric analysis and finalise a module that will be suitable in the assessment of radiation induced proctitis. [Copyright &y& Elsevier]

Abstract: Background and purpose: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated. Material and methods: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA–IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT). Results: At a median follow-up of 27.6months (range 4–233months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p =0.015; HR: 0.45; 95%CI: 0.24–0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p =0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04–18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild. Conclusion: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity. [Copyright &y& Elsevier]