Integrated breast conservation and intraoperative radiation therapy

Summary The introduction of innovative radiotherapy approaches for early breast cancer patients is rapidly changing the radiation oncologists' attitude and their expectations to obtain a good local control while decreasing morbidity therefore improving patient's quality of life. Intraoperative radiotherapy is a very attractive treatment modality in the multidisciplinary approach to breast conservation as is testified by the rapidly growing number of patients accrued in numerous studies all over Europe since 2000. A major advantage of intraoperative radiotherapy in breast cancer treatment is the administration of a large dose of radiation directly to the tumour bed, avoiding the possible geographic miss. Accurate localization and precise definition of the tumour bed volume is essential to achieve maximal efficacy in terms of local control while minimizing unnecessary damage to the normal breast tissue. Intraoperative radiotherapy reduces radiation exposure of the skin, lung, heart and normal subcutaneous tissues thus contributing to the low incidence of side effects and the generally excellent cosmetic results. Compared to other intraoperative techniques, the superiority of intraoperative radiotherapy appears to be the high homogeneity of dose distribution. The linear quadratic model used to calculate the biologic equivalent dose of intraoperative radiotherapy treatments for both tumour and normal tissue effects, is not considered totally reliable for large dose per fraction. The main concern is the potential increase in severe late side effects. Conversely, we expect an enhanced local control due to the radiobiologic efficacy of a large single dose delivered soon after tumour excision, with an immediate cell killing effect over any potential microscopic disease. The advantage of shortening the overall treatment time is that it avoids any delay in the administration of chemotherapy. The safety of intraoperative radiotherapy as a treatment modality in the context of breast conservation has been proved but conclusive data on local control and survival are expected from long term results of the ongoing studies

Conventional and Algorithmic Music Listening before Radiotherapy Treatment: A Randomized Controlled Pilot Study

Music listening is a widespread approach in the field of music therapy. In this study, the effects of music listening on anxiety and stress in patients undergoing radiotherapy are investigated. Sixty patients with breast cancer who were candidates for postoperative curative radiotherapy were recruited and randomly assigned to three groups: Melomics-Health (MH) group (music listening algorithmically created, n = 20); individualized music listening (IML) group (playlist of preferred music, n = 20); no music group (n = 20). Music listening was administered for 15 min immediately before simulation and during the first five radiotherapy sessions. The State-Trait Anxiety Inventory (STAI) and the Psychological Distress Inventory (PDI) were administered before/after treatment. Cochran’s Q test and McNemar test for paired proportions were performed to evaluate if the proportion of subjects having an outcome score below the critical value by treatment and over time was different, and if there was a change in that proportion. The MH group improved in STAI and PDI. The IML group worsened in STAI at T1 and improved STAI-Trait at T2. The IML group worsened in PDI at T2. The No music group generally improved in STAI and PDI. Clinical and music listening-related implications are discussed defining possible research perspectives in this field

A co-culture method to investigate the crosstalk between X-ray irradiated caco-2 cells and PBMC

The protocol adopted in this work aims at unraveling how X-rays perturb the functioning of the intestinal barrier, focusing on the interplay between colorectal tumor cells and the immune system. Colorectal carcinoma is among the most common type of cancer, typically treated by surgery, chemotherapy, and radiotherapy. Advantages of radiotherapy in targeting the tumor are well known. However, even limited exposures of healthy tissues are of great concern, particularly regarding the effects on the intestinal barrier and the immune system. The adopted setup allows to study the interplay between two cell populations in a condition more similar to the physiological one, when compared to normal cell cultures. For this purpose, we resort to different techniques and we used an in vitro co-culture model, based on Caco-2 cells differentiated as a monolayer and PBMC, sharing the same culture medium. This protocol has been developed to focus on both macroscopic effects, i.e. cell viability and Trans-Epithelial Electrical Resistance (TEER), and, through western blot, molecular alterations, i.e. the activation of inflammatory pathway in immune cells and the tight junction protein expression in Caco-2 cells. Initial evaluation of radiation effects on Caco-2 cell viability was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Trypan blue assays, while TEER was measured at fixed time intervals through an ohmmeter specifically designed for co-culture systems. In this way, the effects due to radiation, the presence of Peripheral Blood Mononuclear Cells (PBMC), and eventually their synergistic effect, can be demonstrated. Through these complementary techniques, we observed a high radio-resistance of Caco-2 within the range of 2 - 10 Gy of X-rays and an increased Caco-2 monolayer permeability when PBMCs were added. In particular, PBMC presence was found to be associated with the variation in the tight junction scaffold proteins expression

Surrogate-driven deformable motion model for organ motion tracking in particle radiation therapy

International audienceThe aim of this study is the development and experimental testing of a tumor tracking method for particle radiation therapy, providing the daily respiratory dynamics of the patient's thoraco-abdominal anatomy as a function of an external surface surrogate combined with an a priori motion model. The proposed tracking approach is based on a patient-specific breathing motion model, estimated from the four-dimensional (4D) planning computed tomography (CT) through deformable image registration. The model is adapted to the interfraction baseline variations in the patient's anatomical configuration. The driving amplitude and phase parameters are obtained intrafractionally from a respiratory surrogate signal derived from the external surface displacement. The developed technique was assessed on a dataset of seven lung cancer patients, who underwent two repeated 4D CT scans. The first 4D CT was used to build the respiratory motion model, which was tested on the second scan. The geometric accuracy in localizing lung lesions, mediated over all breathing phases, ranged between 0.6 and 1.7 mm across all patients. Errors in tracking the surrounding organs at risk, such as lungs, trachea and esophagus, were lower than 1.3 mm on average. The median absolute variation in water equivalent path length (WEL) within the target volume did not exceed 1.9 mm-WEL for simulated particle beams. A significant improvement was achieved compared with error compensation based on standard rigid alignment. The present work can be regarded as a feasibility study for the potential extension of tumor tracking techniques in particle treatments. Differently from current tracking methods applied in conventional radiotherapy, the proposed approach allows for the dynamic localization of all anatomical structures scanned in the planning CT, thus providing complete information on density and WEL variations required for particle beam range adaptation

Immunophenotyping Reveals No Significant Perturbation to PBMC Subsets When Co-cultured With Colorectal Adenocarcinoma Caco-2 Cells Exposed to X-Rays

In vitro co-culture models between tumor cells and peripheral blood mononuclear cells (PBMCs) allow studying the interplay between these cell populations, potentially gaining insight into the in vivo response of the immune system to the presence of the tumor, as well as to possible other agents as radiation used for therapeutic purposes. However, great care is needed in the experimental optimization of models and choice of conditions, as some setups might offer a limited possibility to capture subtle immune perturbations. A co-culture model of PBMCs from healthy donors and colorectal adenocarcinoma Caco-2 cells was successfully adopted in a previous work to measure effects on Caco-2 and modulation of signaling when these latter are irradiated. We here tested if the same experimental setting allows to measure perturbations to the main PBMC subsets: we performed immunophenotyping by means of flow cytometry and quantified helper and cytotoxic T cells, NK cells, and B cells, when PBMCs are cultured alone (control), in presence of non-irradiated Caco-2 cells or when these latter are exposed to a 10 Gy X-ray dose from a conventional radiotherapy accelerator. To measure a baseline response in all experimental conditions, PBMCs were not further stimulated, but only followed in their time-evolution up to 72 h post-irradiation of Caco-2 and assembly of the co-culture. In this time interval PBMCs maintain a high viability (measured via the MTT assay). Caco-2 viability (MTT) is slightly affected by the presence of PBMCs and by the high radiation dose, confirming their radioresistance. Immunophenotyping results indicate a large inter-individual variability for different population subsets already at the control level. We analyzed relative population changes and we detected only a small but significant perturbation to cytotoxic T cells. We conclude that this model, as it is, is not adequate for the measurements of subtler immune perturbations (if any, not washed-out by inter-individual differences). For this purpose, the model needs to be modified and further optimized e.g., including a pre-treatment strategy for PBMCs. We also performed a pooled analysis of all experimental observations with principal component analysis, suggesting the potential of this tool to identify subpopulations of similarly-responding donors

CYBERKNIFE ROBOTIC IMAGE-GUIDED STEREOTACTIC RADIOTHERAPY FOR ISOLATED RECURRENT PRIMARY, LYMPH NODE OR METASTATIC PROSTATE CANCER

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Radiotherapy for oligometastatic cancer: a survey among radiation oncologists of Lombardy (AIRO-Lombardy), Italy

AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials