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

Perturbation of specific transcripts in peripheral blood mononuclear cells in breast cancer: a case control pilot study

Introduction: Breast cancer (BC) is the most common type of diagnosed cancer worldwide and the leading cause of cancer death in women and it is the second most frequent cancer-causing mortality for women worldwide. Peripheral blood-based biopsy for BC could be a promising tool for risk prediction and diagnosis. In this study, we aimed to evaluate the gene expression profile of PBMCs in Italian patients with BC. Methods: In this case-control pilot study, we isolated PBMCs from 22 BC patients and 21 healthy controls and evaluated the expression of a panel of 52 target genes related to BC or circadian rhythm by a customized TaqMan Open Array Real-Time PCR panel. Results: Among the differentially expressed genes, 22 remained unchanged. These unchanged genes are mainly involved in cellular processes, including the circadian clock, cellular responses to stress/stimuli, the immune system, signal transduction, and metabolism. We found a total of 30 significantly de-regulated genes. In particular, 8 genes, including PARP6, IGFR1, EZH2, VEGFA, NOTCH1, CD44, BCAR1, and CD24A, resulted significantly down-regulated in patients with BC compared to Controls, while 22 genes were significantly up-regulated in BCs patients compared to Controls. We found several already reported BC-associated genes up-regulated in PBMCs of our BC patients, but FOXO3, ARNTL, and ADAM17 emerged as the most strongly up-regulated. The enrichment pathways analysis highlight that de-regulated genes are mainly involved in the regulation of gene expression and transcription, signal transduction, and immune system response. Discussion: The results of our pilot study demonstrated that the evaluation of PBMC gene signature could be a valuable tool for primary prevention and early diagnosis of BC in several high-risk settings, thus reducing the global mortality associated with this tumour. Take-home message: Non-invasive screening programs, particularly those adopted in workplaces, may have a great impact on early diagnosis and good prognosis for BC. Our study provided proof of concept that the development of a screening test based on PBMC-derived gene expression biomarkers could be a viable route

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

Intensity-Modulated Radiotherapy in the Treatment of Pancreatic Adenocarcinoma – A Review

Pancreatic cancer remains one of the leading causes of cancer deaths. Despite improvements in imaging, surgical techniques, chemotherapy agents, and radiation techniques, the prognosis for patients with pancreatic adenocarcinoma remains poor. Traditionally, radiotherapy (RT) has been utilized as neoadjuvant, adjuvant, or definitive treatment, and represents an important therapeutic option in pancreatic adenocarcinoma. Intensity-modulated radiation therapy (IMRT), a more recent RT technique, has the potential to deliver an adequate dose to the tumour volume with a minimal dose to the surrounding critical structures such as duodenum, small intestine, liver, kidneys, and spinal cord. This article provides a review about the role of IMRT in the treatment of pancreatic cancer, concerning clinical outcomes such as toxicity, local control, and overall survival

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

IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: long term results of an ISIORT pooled analysis

Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy

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