Intensity-modulated radiotherapy and cisplatin-based chemotherapy for anal cancer: long-term outcomes at a single institution.

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.

The Effect of Adjuvant Radiotherapy on One- and Two-Stage Prosthetic Breast Reconstruction and on Autologous Reconstruction: A Multicenter Italian Study among 18 Senonetwork Breast Centres.

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p=0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction. Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered.

A narrative review for radiation oncologists to implement preoperative partial breast irradiation.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454).

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature.

PURPOSE: To critically review available literature on hypofractionated (≥ 3 Gy/fraction) proton therapy (PT) for breast cancer (BCa). METHODS: A systematic screening of the literature was performed in April 2021 in compliance with the preferred reporting items for systematic reviews and meta-analyses recommendations. All full-text publication written in English were considered eligible. Acute and late toxicities, oncological outcomes and dosimetric features were considered for the analysis. RESULTS: Twelve publications met the inclusion criteria; all studies but one focused on accelerated partial breast irradiation (APBI). Eleven works considered post-operative patients, one referred to ABPI as a curative-intent modality. The dosimetric profile of PT compared favorably with both photon-based 3D conformal and intensity-modulated techniques, while a more extended follow-up is warranted to fully assess both the long-term toxicities and the non-inferiority of oncological outcomes. CONCLUSION: Our work shows that results on PT for BCa are currently only available for APBI applications, with dosimetric analyses demonstrating a clear advantage over both 3D conformal and intensity modulated X-rays techniques, especially when ≥ 2 treatment fields were used. However, further evidence is needed to define whether such theoretical benefit translates into clinical improvements, especially in the long-term.

Safety of autologous fat grafting in breast cancer: a multicenter Italian study among 17 senonetwork breast units autologous fat grafting safety: a multicenter Italian retrospective study.

BACKGROUND: Autologous fat grafting (AFG), defined as the re-implant to the breast of fat tissue from different body areas, has been firstly applied to esthetic plastic surgery and then has moved to reconstructive surgery, mainly used for scar correction and opposite breast altering. Nevertheless, due to the potentially unsafe stem-like properties of adipocytes at the tumoral bed level, no clear evidence of the procedure's oncological safety has been clearly documented at present. PATIENTS AND METHODS: We retrospectively collected data of early breast cancer (BC) patients from 17 Italian Breast Units and assessed differences in terms of locoregional recurrence rate (LRR) and locoregional recurrence-free survival (LRFS) between patients who underwent AFG and patients who did not. Differences were analyzed in the entire cohort of invasive tumors and in different subgroups, according to prognostic biological subtypes. RESULTS: With a median follow-up time of 60 months, LRR was 5.3% (n = 71) in the matched population, 3.9% (n = 18) in the AFG group, and 6.1% (n = 53) in the non-AFG group, suggesting non-inferiority of AFG (p = 0.084). Building Kaplan-Meier curves confirmed non-inferiority of the AFG procedure for LRFS (aHR 0.73, 95% CI 0.41-1.30, p = 0.291). The same effect, in terms of LRFS, was also documented among different biological subtypes (luminal-like group, aHR 0.76, 95% CI 0.34-1.68, p = 0.493; HER2 enriched-like, aHR 0.89, 95% CI 0.19-4.22, p = 0.882; and TNBC, aHR 0.61, 95% CI 0.12-2.98, p = 0.543). CONCLUSIONS: Our study confirms in a very large, multicenter cohort of early BC patients that, aside the well-known benefits on the esthetic result, AFG do not interfere negatively with cancer prognosis.

How to Perform Repeat Sentinel Node Biopsy Safely After a Previous Mastectomy: Technical Features and Oncologic Outcomes.

BACKGROUND: The latest National Comprehensive Cancer Network Breast Cancer Guidelines still discourage repeat sentinel node biopsy (SNB) after mastectomy, and the largest multicentric study available reports only 35 cases in the absence of previous axillary dissection (AD). METHODS: From January 2003 to November 2018, 89 patients of the European Institute of Oncology with local recurrence of breast cancer after mastectomy, free of distant metastases, with a clinically negative axilla and a negative axillary ultrasound, in absence of AD, underwent lymphatic mapping before wide local excision. RESULTS: During surgery, SNB was successful for 99% of the patients, with 14% being metastatic. Additional metastatic nodes removed by AD after a positive sentinel node occurred in 82% of cases. After a medium follow-up period of 3.7 years, the overall survival rate was 96.7%, and the disease-free survival rate was 84.4%. No axillary relapse after AD was recorded. One patient who refused human epidermal growth factor receptor 2 (HER2)-targeted treatment experienced ipsilateral axillary recurrence after a negative repeat SNB. The first axillary level was never directly irradiated because all the patients with positive repeat SNB underwent AD. For invasive luminal-like HER2-negative recurrences, the metastatic sentinel node was significantly associated with the choice to prescribe adjuvant chemotherapy (p = 0.003). CONCLUSIONS: In specialized centers, repeat axillary SNB for patients with local recurrence after mastectomy in the absence of previous AD can represent a safe option for detection and removal of occult axillary disease that would otherwise not be excised/irradiated to achieve better local control and could possibly influence the choice of adjuvant treatments.

Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study - a phase I/II clinical trial protocol.

BACKGROUND: Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients. METHODS: This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate. DISCUSSION: The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale. TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov ( NCT04679454 ).

Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial.

BACKGROUND: In the randomised, phase 3 equivalence trial on electron intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI) with the use of intraoperative radiotherapy was associated with a higher rate of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation (WBI) in patients with early-stage breast cancer. Here, we aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial. METHODS: This single-centre, randomised, phase 3 equivalence trial was done at the European Institute of Oncology (Milan, Italy). Eligible women, aged 48-75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative WBI with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year IBTR rate of 3% in the WBI group and equivalence of the two groups, if the 5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess, corresponding to 7·5%. Overall survival was the secondary endpoint. The main analysis was done by intention to treat. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This trial is registered with ClinicalTrials.gov, NCT01849133. FINDINGS: Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12·4 years (IQR 9·7-14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68-7·95, p<0·0001). In the ELIOT group, the 5-year IBTR rate was 4·2% (95% CI 2·8-5·9), the 10-year rate was 8·1% (6·1-10·3), and the 15-year rate was 12·6% (9·8-15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95% CI 0·1-1·3), the 10-year rate was 1·1% (0·5-2·2), and the 15-year rate was 2·4% (1·4-4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77-1·36, p=0·85). In the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1-97·9) at 5 years, 90·7% (88·2-92·7) at 10 years, and 83·4% (79·7-86·4) at 15 years; and in the WBI group, the overall survival rate was 96·8% (95·1-97·9) at 5 years, 92·7% (90·4-94·4) at 10 years, and 82·4% (78·5-85·6) at 15 years. We did not collect long-term data on adverse events. INTERPRETATION: The long-term results of this trial confirmed the higher rate of IBTR in the ELIOT group than in the WBI group, without any differences in overall survival. ELIOT should be offered to selected patients at low-risk of IBTR. FUNDING: Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, Umberto Veronesi Foundation, American Italian Cancer Foundation, The Lombardy Region, and Italian Ministry of Health.

Mastectomy alone for pT1-2 pN0-1 breast cancer patients: when postmastectomy radiotherapy is indicated.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy.

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.

Multicentric breast cancer with heterogeneous histopathology: a multidisciplinary review.

Multiple synchronous (multifocal or multicentric) ipsilateral breast cancers with heterogeneous histopathology are a rare clinical occurrence, however, their incidence is increasing due to the use of MRI for breast cancer screening and staging. Some studies have demonstrated poorer clinical outcomes for this pattern of breast cancer, but there is no evidence to guide clinical practice. In this multidisciplinary review, we reflect on pathology and molecular characteristics, imaging findings, surgical management including conservation and reconstructive options and approach to the axilla, and the role of chemotherapy and radiotherapy. Multidisciplinary discussions appear decisive in planning an appropriate surgical choice and defining the correct systemic treatment tailored to each clinical condition.

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Dosimetric study to assess the feasibility of intraoperative radiotherapy with electrons (ELIOT) as partial breast irradiation for patients with cardiac implantable electronic device (CIED).

PURPOSE: To report in-vivo dosimetry in the infraclavicular region, a potential site of a cardiac implantable electronic device (CIED) and to evaluate the absorbed dose from intraoperative radiotherapy with electrons (ELIOT). METHODS: 27 non-cardiopathic breast cancer (BC) patients without CIED received quadrantectomy and ELIOT as partial breast irradiation. Before delivering ELIOT, two catheters, each containing eight thermoluminescent dosimeters (TLDs), were positioned in the infraclavicular region. TLDs internal catheter was located deep in the tumor bed while the external catheter was placed on patient's skin. RESULTS: Data were available for 24/27 patients. The absorbed doses were referred to the dose of 21 Gy. Values measured by the external catheter were low, although statistically significant higher doses were found close to the applicator (mean values 0.26-0.49 Gy). External TLD doses in proximity of the applicator were lower than those detected by their internal counterparts. Values measured by the internal catheter TLDs varied according to the distance from the applicator while no correlation with tumor site and beam energy was found. The distance from the applicator to deliver < 2 Gy to a CIED was 2 cm, while from 2.5 cm the dose measured in all the patients became negligible. CONCLUSIONS: This dosimetric study provided data to support the clinical use of ELIOT in BC patients having CIEDs as long as the suggested minimum safe distance of 2.5 cm is taken from the RT field in case of ELIOT single dose of 21 Gy, in the energy range of 6-10 MeV.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS.

Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46-62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49-0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42-0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33-0.77 versus HR = 0.84, 95% CI: 0.60-1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

The 2016 Assisi Think Tank Meeting on breast cancer: white paper.

PURPOSE: To identify weak points in daily routine use of radiation therapy (RT) for non-metastatic breast cancer patients, particularly when data are lacking or equivocal, a "think tank" of experts met in Assisi. METHODS: Before the meeting, controversial issues on non-metastatic breast cancer were identified and reviewed, and clinical practice investigated by means of an online questionnaire. During the 3-day meeting, topics were discussed in-depth with attendees and potential sponsors that are involved in breast cancer treatment. RESULTS: Three issues were identified as needing further investigation: (1) Regional lymph node treatment in early-stage breast cancer; (2) Combined post-mastectomy RT and breast reconstruction; (3) RT in patients treated with primary systemic therapy. Future research proposals included the following: (1) Participating in appropriately selected on-going clinical trials; (2) Designing new randomized controlled clinical trials and prospective population cohort studies; (3) Setting-up large database(s) to generate predictive response models and detect biomarkers for tailored loco-regional treatments. CONCLUSIONS: It is hoped that the ATTM findings, as described in the present white paper, will stimulate a new generation of radiation oncologists to focus on research in these areas, and that the white paper will become a tool for multidisciplinary groups to help them design research proposals and strategies.

MR Imaging for Selection of Patients for Partial Breast Irradiation: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review articles that estimated the ineligibility for partial breast irradiation (PBI) after magnetic resonance (MR) imaging. MATERIALS AND METHODS: No ethics committee approval was needed. A systematic search was performed by using MEDLINE and EMBASE. The rate of patients eligible at standard assessment (ie, clinical examination, mammography, and/or ultrasonography) but ineligible after MR imaging was a study outcome. Odds ratios (ORs) were calculated to identify predictors. Quality was appraised by using the Strengthening Reporting of Observational Studies in Epidemiology checklist. RESULTS: Of 93 retrieved articles, six were included (total, 3136 patients). For PBI eligibility, all studies applied National Surgical Adjuvant Breast and Bowel Project B-39 criteria. Ineligibility at standard assessment varied from 21% to 80%; MR imaging prompted ineligibility for PBI in 6%-25% of patients who were initially deemed eligible or in 2%-20% if calculated on the overall number of patients initially screened. Meta-regression showed a negative correlation between ineligibility at standard assessment and ineligibility after MR imaging (P < .001). The pooled percentage of patients eligible at standard assessment but ineligible after MR imaging was 11% (95% confidence interval [CI]: 6%, 19%). Predictors for ineligibility after MR imaging were cancers stage pT2 or greater versus less than stage pT2 (OR, 8.8 [95% CI: 4.7, 16.7]; P < .001), invasive lobular histopathologic results versus invasive ductal pathologic results (OR, 3.0 [95% CI: 1.6, 6.6]; P = .007), pre- versus postmenopausal status (OR, 1.9 [95% CI: 1.3, 2.6]; P < .001), invasive cancer versus ductal carcinoma in situ (OR, 1.6 [95% CI: 1.0, 2.4]; P = .031). Study quality ranged from 17 to 20 (maximum quality, 22). The risk of publication bias was moderate. CONCLUSION: One of nine women (11%), who on the sole basis of standard assessment were candidates to undergo PBI, was found to be ineligible after undergoing MR imaging. Breast MR imaging should be used to select patients for PBI.