Sofia Rivera

Four years with FALCON - an ESTRO educational project: achievements and perspectives.

Variability in anatomical contouring is one of the important uncertainties in radiotherapy. FALCON (Fellowship in Anatomic deLineation and CONtouring) is an educational ESTRO (European SocieTy for Radiation and Oncology) project devoted to improve interactive teaching, the homogeneity in contouring and to compare individual contours with endorsed guidelines or expert opinions. This report summarizes the experience from the first 4 years using FALCON for educational activities within ESTRO School and presents the perspectives for the future.

First results of the preoperative accelerated partial breast irradiation (PAPBI) trial

BACKGROUND AND PURPOSE The aim of this study is to assess the toxicity and cosmetic outcome of preoperative accelerated partial breast irradiation (PAPBI) for breast cancer patients with low risk on local recurrence. MATERIAL AND METHODS Women aged ⩾60years with an invasive, unifocal ⩽3cm on MRI, (non-lobular) adenocarcinoma of the breast and a negative sentinel node received PAPBI (40Gray in 10 fractions over 2 weeks). Six weeks after radiotherapy a wide local excision was performed. RESULTS 70 patients with a median follow-up of 23 months (3-44 months) were evaluated. The overall postoperative infection rate was 11%. At 1, 2 and 3 years of follow-up respectively 89%, 98% and 100% of patients had no or mild induration-fibrosis. Fibrosis was only found in a small volume of the breast. The global cosmetic outcome was good to excellent in 77% at 6 months to 100% at 3 years. Two patients developed a local recurrence. CONCLUSION Our first results show limited fibrosis in a small volume and good to excellent cosmetic outcome. In selected patients, preoperative radiotherapy appears to be a good option for breast conserving therapy.

Mise au pointRadiothérapie axillaire prophylactique des cancers du seinProphylactic axillary radiotherapy for breast cancer

Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk-benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy.

Salvage high-dose-rate brachytherapy for esophageal cancer in previously irradiated patients: A retrospective analysis

PURPOSE To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer. METHODS AND MATERIALS We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5-7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume. RESULTS Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (<10%) before salvage brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%). CONCLUSIONS Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy.

Association of radiotherapy and hormonotherapy in locally advanced prostate cancer

Combination of radiotherapy and androgen deprivation is now considered as the standard of care for patients with a localized prostate cancer but poor prognostic factors. Two groups of randomized trials have led to this recommendation. Some have compared radiotherapy alone versus hormonal treatment and radiotherapy: these trials demonstrated, now with a long follow-up, an improvement in 10-year survival for the combined treatment. Three recent trials compared androgen deprivation alone or combined with radiotherapy; a benefit in survival was also demonstrated in favour of the combination. Some questions remained concerning the optimal duration of hormonal treatment, in view of its potential side effects. Patients in the intermediate prognostic groups could receive a short-term androgen deprivation, but those with a high Gleason score must be treated with a long-term hormonal treatment. Modalities of radiotherapy, regarding volumes and dose must also be precised in the next years.

Individualizing Adjuvant Radiotherapy in Patients With Breast Cancer: Let's Not Get Ahead of Ourselves

ative Group (EBCTCG) overview 2 and represents about 3.5% of the worldwide randomized experience. The latter study identified four independent prognostic factors of recurrence: age, histological grade, surgical resection extent, and estrogen receptor status/tamoxifen treatment. Curiously, Wickberg et al provide results in terms of all recurrences adopting a similar definition of that used in the overview. However, in the worldwide studies this definition was related to the fact that several trials only registered the first recurrence and not the

PO-0952: Blended teaching reduces interobserver contouring variability: first results of the FALCON project

S463 ________________________________________________________________________________ system towards or away from the isocentre position, which is defined by the isocentre of the MRI scanner. The rail system enables the linatron to be placed at 8 different positions from the linatron ranging from a SSD of 190-336cm. To verify alignment of the radiation beam for the different linac rail positions, radiation profiles were acquired in air at different distances from the target. From the profiles the central axis position (CAX) was used to establish the alignment of the radiation beam. To verify MLC alignment to the CAX without the ability to rotate the collimator, a series of half blocked fields were used, with abutting fields and picket fence tests used to verify positional accuracy. Standard scanning water tank systems can not be used within the MRI scanner due to both ferromagnetic components and lack of physical space. To enable a comparison of baseline data once the magnet is installed, water dosimetry measurements were compared with measurements within an adjustable solid water phantom.

New challenge of developing combined radio-drug therapy

Combined modality treatment can be used to improve control of the local disease at the expense of increased toxicity. Several randomized trials have demonstrated that this combined modality therapy is better than radiotherapy alone or chemotherapy alone in the treatment of locally advanced diseases. Several new targets as well as potential new radio-sensitizers have been identified. To speed-up the process of developing new combined modality treatments, good preclinical models for optimization of the ratio between efficacy and toxicity and a well established methodology within a network of advanced high-tech laboratories and clinical departments devoted to early phase trials, are mandatory. The Synergy of Targeted Agents and Radiation Therapy (STAR) platform of the European Organisation for Research and Treatment of Cancer (EORTC) is gathering these tools.

Abstract C220: Combining novel targeted therapies and radiotherapy: A challenge to overcome.

Radiotherapy is a major cancer treatment modality involved in 50% of cancer treatments and 40% of cancer cure. Modern radiotherapy techniques such as Intensity Modulated Radiation Therapy (IMRT) and high precision image guided radiotherapy (IGRT), as well as dose escalation strategies to limited volumes, have demonstrated not only improved effectiveness but also reduced toxicity. Despite these advances, loco-regional relapse remains an issue. Opportunities to further improve loco-regional disease control and cure rates lay in molecularly targeted therapies that combine radiotherapy with targeted agents. Such novel combination strategies should preferably result in the specific radio-sensitization of tumors and/or provide normal tissue protection. Increasing knowledge in understanding the molecular and cellular response to ionizing radiation and genetic alteration in tumors enabled the development of novel drug-radiotherapy combinations strategies of which some have already started to affect the outcome after radiotherapy. Promising agents and drug classes for such radiotherapy combination strategies have been identified and include DNA damage response pathways inhibitors, PI3K-AKT pathway inhibitors, hypoxia modifiers or epigenetic modulators. However, despite these opportunities and strong rationales, less than 40 phase III trials combining novel agents with radiotherapy have been published to date and drugs are often tested for radiotherapy combinations late in their development. The variation in possible radiotherapy sites, settings and schedules, the complexity of such approaches, lack of expertise and the shortage of successful examples may cause the procrastination. In conclusion, novel radiotherapy combination strategies are highly promising and the challenges of combining targeted therapies and radiotherapy need to be overcome. By the implementation of a robust methodology while rigorously assessing the potential benefits and toxicities of the possible combinations in relevant preclinical models we propose to establish a comprehensive development strategy that aims at clinical translation in the most promising settings. A stringent evaluation early in the development that will help to prioritize radiotherapy settings, agents and tumor sites could be realized in a collaboration of academic institutions, collaborative groups and industry. With the objective to foster the development of these combined treatments the EORTC ROG has created a working group that established and coordinates a unique European multicentric platform. Providing state-of-the-art clinical and preclinical radiotherapy modalities, molecular diagnostic tools and imaging platforms it integrates the expertise of different radiobiology and radio-oncology centers, to define research strategies from proof of concept to clinical trials. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C220. Citation Format: Sofia Rivera, Conchita Vens, Philippe Maingon, Anne Sophie Govaerts, Emad Shash, Denis Lacombe, Warren Grant, Vincent Gregoire. Combining novel targeted therapies and radiotherapy: A challenge to overcome. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C220.

Abstract OT2-1-03: Preoperative accelerated partial breast irradiation trial (PAPBI); defining radiosensitivity

Background and aim of the study: A.The ongoing Preoperative Accelerated Partial Breast Irradiation (PAPBI) trial (NCT01024582) is based on the rationale that three-dimensional conformal external-beam radiation (3D-CRT) leads to more dose homogeneity compared with brachy-or intraoperative radiotherapy (RT). By irradiating preoperatively this can lead to more accurate tumor delineation and smaller irradiated volumes. As the tumor remains in situ during irradiation, more precise delivery of the radiation dose is guaranteed with CT cone beam linear accelerators, avoiding the uncertainties of the original tumor position in the operation cavity as is the case in postoperative RT. Tumor excision 6 weeks after RT removes the high dose volume tissue and can lead to better cosmesis. B. By assessing tumor response to radiotherapy, an additional goal of the study is to develop a gene expression profile that predicts breast cancer radiosensitivity. This gene signature of breast radiosensitivity would further design optimal treatment strategies for individual breast cancer patients treated with BCT. Inclusion citeria : Patients 60 years or older with a cT To study radiosensit ivity, gene expression profiling from RNA and DNA isolated from biopsies (mRNA gene expression profiles, the miRNA expression profiles and the DNA copy number changes) taken of the tumor before radiotherapy and at time of surgery will be correlated with response to radiotherapy, defined as pathologic response at the time of the lumpectomy. Response of the tumor will be evaluated by MRI scan and PET (before radiotherapy and before surgery) and classical pathology. Endpoint : The main objective is to investigate the impact of a short fractionated schedule given preoperatively on cosmesis and breast fibrosis. Therefore, it is anticipated that the percentage of moderate or severe fibrosis will decrease from 27% as found in the boost arm of the EORTC boost-no boost trial to 15% (Collette et al EJC 2008). The total sample size of 120 patients will provide in excess of 80% power to detect the difference between the null hypotheses (a rate of fibrosis of 27%) and the alternative hypothesis (a rate of fibrosis of 15%) with an exact binomial test at 0.05 2-sided significance level. In addition, the 2-sided 95% confidence interval for the proportion of patients without local recurrence will extend 0.035 from the observed proportion for an expected proportion of 96%. An additional objective is to build a classifier (genomic or proteomic or any kind of molecular signature) to identify responders and non-responders. A total of 120 patients will be included in the study. The main analysis will include 60 patients in the training set and 60 in the validation set. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-1-03.