Pattern of practice of re-irradiation for ipsilateral breast tumor recurrence in Italy: a survey by the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

Purpose The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. Methods In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists’ (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. Results Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed “curative” re-RT for IBTR during the previous two years (2019–2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. Conclusions About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field (AU)

Pattern of practice of re-irradiation for ipsilateral breast tumor recurrence in Italy: a survey by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. METHODS: In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. RESULTS: Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed "curative" re-RT for IBTR during the previous two years (2019-2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. CONCLUSIONS: About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field.

Impact of inter-observer variability on first axillary level dosimetry in breast cancer radiotherapy: An AIRO multi-institutional study.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT.

Radiotherapy of orbital metastases: a systematic review of management and treatment outcomes on behalf of palliative care study group of Italian association of radiotherapy and clinical oncology (AIRO).

OBJECTIVES: We search the current literature on data regarding the role of RT in OM treatment, focusing on the improvement of symptoms and patient quality of life. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. RESULTS: From 340 citations, 60 papers were finally selected: 45 case reports and 15 case series. The case reports accounted for 47 patients. In 37/39 cases (95%), EBRT was done. Patients were mainly treated with 3DCRT, IMRT, and with SBRT. The most used RT regimens were 30 Gy in 10 fractions (23%) and 20-25 Gy in 5 fx (13%). No sever toxicity was reported. A median LC of 11 months (range 1-54 months) and a median OS of 12 months (range 1-54 months) were registered. Among the case series, a total of 457 patients were examined, 227 of whom underwent RT. The main used techniques were 3DCRT, CK, GK, SBRT, and BRT. RT doses could vary from 30 Gy/10 fractions to 60 Gy/30 fractions, 50 Gy/5 fractions, or 16.5-21 Gy in single fraction. No toxicity above G2 was reported. ORR could vary between 75 and 100%. Only two study provided information on response duration: a mean LC time of 22.8 months and a mean time to local progression of 5 months (range: 3-7). Regarding OS, the data were heterogeneous, ranging between 1 and 54 months. CONCLUSIONS: RT for OM seems to be a safe and feasible option. More information on the RT ideal techniques and dose are still needed. ADVANCES IN KNOWLEDGE: This paper tried to sum up the few and fragmented data on the use of radiotherapy for orbital metastases: the possible option ranged from 3D- and 2D-CRT to SBRT, CK, and GK, with different possible fractionations (30Gy in 10 fractions, 60 Gy/30 fractions, 20-50 Gy/5 fractions, or 16.5-21 Gy in single fraction). Regardless of the chosen approach, almost all treated patients experienced a benefit after RT in terms of OM-related symptom intensity reduction and a good acute and late toxicity profile.

Reirradiation on spine metastases: an Italian survey on behalf of palliative care and reirradiation study groups of Italian association of radiotherapy and clinical oncology (AIRO).

AIM: This survey derived from the collaboration between the Palliative Care and Reirradiation Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Its aim was to obtain a real "snapshot" on the treatments of spinal metastases, focusing on reirradiation, among radiation oncologists in Italy. METHODS: The survey was elaborated on SurveyMonkey's online interface and was sent via e-mail to all Radiation Oncologists of AIRO that were invited to anonymously fill in the electronic form within 60 days. The questionnaire was prepared by the AIRO "Palliative care" and "Reirradiation" Study Groups and it consisted of 36 questions, 19 single-choice questions, 10 multiple-choice questions and 6 open questions. The data were analyzed and represented with tables and graphs. RESULTS: The survey shows that palliative radiotherapy remains a field of interest for most ROs in the Italian centers. 3D Conventional Radiation Therapy (3DCRT) alone or in combination with other techniques is the primary choice for patients with a life expectancy of less than 6 months. For patients with a life expectancy of more than six months, there is an increased use of new technologies, such as Volumetric Modulated Arc Therapy (VMAT). Factors considered for retreatment are time between first and second treatment, dose delivered to spine metastasis and spinal cord in the first treatment, vertebral stability, symptoms, and/or performance status. The most feared complication are myelopathy followed by vertebral fracture and local recurrence. This explain an increasing focus on patient selection and the use of high technology in the treatment of metastatic patients. CONCLUSION: Stereotactic body radiotherapy (SBRT) and image-guided radiotherapy allow the administration of ablative RT doses while sparing the constraints of healthy tissue in spinal metastases. However, there is still an unclear and heterogeneous reality in the reirradiation of spinal metastases. A national registry with the aim of clarifying the most controversial aspects of vertebral metastasis retreatments will enable better management of these patients and design more targeted study designs.

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting.

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.

Patterns of Care for Breast Radiotherapy in Italy: Breast IRRadiATA (Italian Repository of Radiotherapy dATA) Feasibility Study.

Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.

Hypofractionated Whole Breast Irradiation and Boost-IOERT in Early Stage Breast Cancer (HIOB): First Clinical Results of a Prospective Multicenter Trial (NCT01343459).

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.

Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience.

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12-109 months). At 5 years, in-field LC was 99.2% (95% CI: 98-99.7); out-field LC 98.9% (95% CI: 97.4-99.6); DFS 96.2% (95% CI: 94.2-97.6); OS 98.6% (95% CI: 97.2-99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.

Hypofractionated breast irradiation: a multidisciplinary review of the Senonetwork study group.

The multidisciplinary management represents a crucial part of the care for cancer patients, resulting in better clinical and process outcomes, with evidence of improved survival among different cancer primary sites, including breast. According with international recommendations established by the European Society of Breast Cancer Specialists (EUSOMA), all breast-cancer patients have to be evaluated by a multidisciplinary team including radiologist, pathologist, surgeon, medical oncologist and radiation oncologist. Thus, variations in clinical practice of each specialty should be discussed and shared with all team members to guarantee a fruitful cooperation among the involved specialists. During the last decades, radiation treatment was deeply changed by the evidence-based adoption of hypofractionated radiotherapy (HFRT) as standard of treatment in patients with early-stage breast cancer undergoing conservative surgery. Moreover, mature randomized data have showed that partial breast irradiation (PBI) is an effective and safe alternative to whole breast irradiation in selected patients with low-risk early-stage breast cancer. Based on this background, we reviewed indications and critical issues of HFRT and PBI analyzing impact of their adoption from a multidisciplinary perspective.

Omission of adjuvant radiotherapy for older adults with early-stage breast cancer particularly in the COVID era: A literature review (on the behalf of Italian Association of Radiotherapy and Clinical Oncology).

This review is aimed at evaluating whether radiation therapy (RT) can be omitted in older adult early-stage low-risk breast cancer (BC) patients. The published data are particularly relevant at present, during the COVID-19 pandemic emergency, to define a treatment strategy and to prioritize essential therapy. Cochrane Database of Systematic Reviews and PubMED were systematically researched from outset through April 2020 using Mesh terms. Only randomized controlled trials (RCT), with one arm without adjuvant whole-breast irradiation (WBI), were included in the analysis. Recent literature regarding the COVID pandemic and BC RT was assessed. The reported RCTs identified a group of BC patients (pT1-2N0M0 R0, grade 1-2, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative tumours) in which the absolute risk of local recurrence (LR) was considered low enough to omit RT. The most common risk factors were tumor diameter, nodal and receptor status. Adjuvant RT had a significant impact on LR but not on distant metastasis (DM) or death. During the COVID 19 pandemic, results from RTCs were re-considered to define treatment recommendations for BC patients. International scientific societies and radiation oncology experts suggested RT omission, whenever possible, in older adult early-stage BC patients. Adjuvant RT might be omitted in a highly selected group of older adult early-stage BC patients with favourable prognostic factors. Hypofractionated regimens should be the standard. RT omission, partial breast irradiation (PBI), and ultra- hypofractionated regimens could be considered in selected cases due to the pandemic.

State of the art in breast intraoperative electron radiation therapy after intraoperative ultrasound introduction.

BACKGROUND: Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation - APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. PATIENTS AND METHODS: B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. RESULTS: From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). CONCLUSIONS: IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study.

BACKGROUND: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). METHODS: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes. RESULTS: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10-16 years). The cumulative risk of IBTR at 5-10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5-10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). CONCLUSION: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Lymph nodal radiotherapy in breast cancer: what are the unresolved issues?

Introduction: Sentinel lymph node biopsy (SLNB) is the gold standard in invasive breast cancer. Axillary dissection (ALND) is controversial in some presentations.Areas covered: Key questions were formulated and explored focused on four different scenarios in adjuvant axillary radiation management in early and locally advanced breast cancer. Answers to these questions were searched in MEDLINE, PubMed from June 1946 to August 2020. Clinical trials, retrospective studies, international guidelines, meta-analysis, and reviews were explored.Expert opinion: Analysis according to biological disease characteristics is necessary to establish the impact of ALND avoidance in unexpectedly positive SLNB (pN1) in cN0 patients. A low-risk probability of axillary recurrence was observed if axillary radiotherapy (ART) or ALND were offered without impact on outcomes. Adjuvant RNI in pT1-3 pN1 treated with mastectomy or BCS should be proposed in unfavorable disease and risk factors. In ycN0 after NACT, SLNB can be offered in selected cases or ALND should be performed. After SLNB post-NACT (ypN1), ALND and adjuvant radiotherapy are mandatory.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

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.

Short course radiotherapy and delayed surgery for locally advanced rectal cancer in frail patients: is it a valid option?

OBJECTIVE: The endpoint of the present study was to evaluate the outcomes of short-course radiotherapy (SCRT) and SCRT with delayed surgery (SCRT-DS) on a selected subgroup of frail patients with locally advanced middle/low rectal adenocarcinoma. METHODS: From January 2008 to December 2018, a total of 128 frail patients with locally advanced middle-low rectal adenocarcinoma underwent SCRT and subsequent restaging for eventual delayed surgery. Rates of complete pathological response, down-staging, disease free survival (DFS) and overall survival (OS) were analyzed. RESULTS: 128 patients completed 5 × 5 Gy pelvic radiotherapy. 69 of these were unfit for surgery; 59 underwent surgery 8 weeks (average time: 61 days) after radiotherapy. Downstaging of T occurred in 64% and down-staging of N in 50%. The median overall survival (OS) of SCRT alone was 19.5 months. The 1-year, 2-year, 3-year and 5-year OS was 48%, 22%, 14% and 0% respectively. In the surgical group, the median disease-free survival (DFS) and median OS were, respectively, 67 months (95% CI 49.8-83.1 months) and 72.1 months (95% CI 57.5-86.7 months). The 1, 2, 3, 5-year OS was 88%, 75%, 51%, 46%, respectively. Post-operative morbidity was 22%, mortality was 3.4%. CONCLUSIONS: Frail patients with advanced rectal cancer are often "unfit" for long-term neoadjuvant chemoradiation. A SCRT may be considered a valid option for this group of patients. Once radiotherapy is completed, patients can be re-evaluated for surgery. If feasible, SCRT and delayed surgery is the best option for frail patients.