Vincent Remouchamps

Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial

BACKGROUND Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001). INTERPRETATION A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. FUNDING Fonds Cancer, Belgium.

ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer

BACKGROUND AND PURPOSE Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. MATERIAL AND METHODS During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. RESULTS Borders of the CTV encompassing a 5mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. CONCLUSION The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency.

An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways.

PURPOSE To develop a protocol for the irradiation of ethmoid sinus cancer, with the aim of sparing binocular vision; of developing a strategy of intensity-modulated radiation therapy (IMRT) planning that produces dose distributions that (1) are consistent with the protocol prescriptions and (2) are deliverable by static segmental IMRT techniques within a 15-minute time slot; of fine tuning the implementation strategy to a class solution approach that is sufficiently automated and efficient, allowing routine clinical application; of reporting on the early clinical implementation involving 11 patients between February 1999 and July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer patients were enrolled in the study. For Patients 1-8, a first protocol was implemented, defining a planning target volume prescription dose of 60 to 66 Gy in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted (now considered mature) protocol was implemented, defining a (planning target volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS The class solution-directed strategy developed during this study reduced the protocol translation process from a few days to about 2 hours of planner time. The mature class solution involved the use of 7 beam incidences (20-37 segments), which could be delivered within a 15-minute time slot. Acute side effects were limited and mild. None of the patients developed dry eye syndrome or other visual disturbances. The follow-up period is too short for detection of retinopathy or optic nerve and chiasm toxicity. CONCLUSION Conventional radiotherapy of ethmoid sinus tumors is associated with serious morbidity, including blindness. We hypothesize that IMRT has the potential to save binocular vision. The dose to the optic pathway structures can be reduced selectively by IMRT. Further enrollment of patients and longer follow-up will show whether the level of reduction tested by the clinical protocol is sufficient to save binocular vision. An adaptive strategy of IMRT planning was too inefficient for routine clinical practice. A class solution-directed strategy improved efficiency by eliminating human trial and error during the IMRT planning process.

Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation

BACKGROUND AND PURPOSE Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI). MATERIALS AND METHODS Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy. RESULTS DIBH was able to reduce (p<0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH (p<0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH. CONCLUSIONS This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI.

Evaluation of a leaf position optimization tool for intensity modulated radiation therapy of head and neck cancer

BACKGROUND AND PURPOSE Since 1996, patients are treated at Ghent University Hospital with a multi-segment technique using MultiLeaf Collimators. The segments were obtained by using the Beams eye view projections of the planning target volume (PTV) and the organs at risk (OARs), after which the segments weights were optimized. To investigate if optimization of the leaf positions would further improve the intensity modulated radiation therapy (IMRT) plans, a tool optimizing leaf positions and segment weights simultaneously, was developed. This tool is called SOWAT, which is the acronym for segment outline and weight adapting tool. MATERIAL AND METHODS The tool evaluates the effects of changing the position of each collimating leaf of all segments on the value of the objective function. Only changes that improve the value of the objective function are retained. Between December 1999 and January 2001, 30 head and neck patients were treated with IMRT. Two patient groups were distinguished: pharyngeal and laryngeal tumors (n=17) and sinonasal tumors (n=13). A specific set of physical endpoints was evaluated for each group. Dose statistics of the treatment plans without and with SOWAT were analyzed. RESULTS When using SOWAT for the pharyngeal and laryngeal cases, the PTV dose homogeneity increased with a median of 11% (range 2-27%), while the maximum dose to the spinal cord was decreased for 14 of the 17 patients. In four plans where parotid function preservation was a goal, the parotid mean dose was lower than 26 Gy in one plan without SOWAT, and in four plans with SOWAT. For the sinonasal tumors, the PTV dose homogeneity increased with a median of 7% (range 1-14%). SOWAT lowered the mean dose to 53 of the 63 optic pathway structures (retina, optic nerve and optic chiasm). SOWAT leaves the number of segments unchanged and has little or no effect on the delivery time. CONCLUSIONS SOWAT is a powerful tool to perform the final optimization of IMRT plans, without increasing the complexity of the plan or the delivery time.

Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial

Importance Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy. Objective The EORTC “boost no boost” trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up. Design, Setting, and Participants Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III “boost no boost” trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years. Interventions No further treatment or 16-Gy boost, after BCS and 50-Gy WBI. Main Outcomes and Measures Time to ipsilateral breast tumor recurrence (IBTR) as first event. Results The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P < .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P < .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high-risk patients (⩽50 years with DCIS present). Conclusions and Relevance The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately. Trial Registration clinicaltrials.gov Identifier: NCT02295033

Vessel based delineation guidelines for the elective lymph node regions in breast cancer radiation therapy - PROCAB guidelines

OBJECTIVE A national project to improve the quality of breast radiation therapy was started, named PROCAB (PROject on CAncer of the Breast). One of the objectives was to reach a national consensus guideline for the delineation of the regional lymph node areas in breast radiation therapy. METHODS The realization of the new guidelines was a step by step process that started with multiple expert meetings where the existing guidelines were analyzed and the delineations of the lymph node regions were performed together with a surgeon, specialized in the anatomy of the drainage of the breast. RESULTS The delineation guidelines are vessel-based. Since the occurrence of pathological lymph nodes is typically around the veins, the cranial and caudal borders of all different nodal regions are based on a 5mm margin around the veins, except for the parasternal lymph node area. Compared to the existing guidelines there are some major changes. CONCLUSION With this project a national as well as a European (ESTRO) consensus guideline for the delineation of the regional lymph node areas in breast RT is reached. The new delineation atlas is vessel-based and no longer field-based.

Prone left-sided whole-breast irradiation: Significant heart dose reduction using end-inspiratory versus end-expiratory gating

PURPOSE To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (PrIN) versus an end-expiratory phase (PrEX). PATIENTS AND METHODS Twenty patients underwent CT-simulation in PrIN and PrEX. Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05Gy in 15 fractions and maximal sparing of the organs at risk. Dose-volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. RESULTS PrIN consistently reduced (P<0.001) heart and left anterior descending coronary artery dose metrics compared to PrEX. Population averages for maximum and mean heart dose were 6.2Gy and 1.3Gy for PrIN versus 21.4Gy and 2.5Gy for PrEX, respectively. Moreover, a maximum heart dose less than 10Gy was achieved in 80% of patients for PrIN. Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. CONCLUSIONS Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation.

PO-0778: Delineation of the regional nodal areas in breast radiotherapy: What are the most problematic regions?

volume delineation. Reasons for non-compliance are mostly problems with target coverage. Thirty-eight percent of the centers reported issues with target coverage; in 1 center they interpret the Dose Volume Histogram differently and are now looking at the 85% coverage of the planning target volume instead of the 95%. Conclusions: The introduction of new delineation guidelines for the RNA in breast radiotherapy has a major impact on the treatment planning and dosimetry with especially introducing newer treatment techniques to achieve better target coverage. Surprisingly, not all centers use the centrally reviewed and corrected target delineation to guide their radiotherapy to the RNA.

294PHYPOFRACTIONATED RADIOTHERAPY REDUCES ACUTE SKIN TOXICITY IN SMALL AND LARGE BREASTED PATIENTS RECEIVING WHOLE-BREAST IRRADIATION

ABSTRACT Aim: Despite the results of large randomized trials in the UK and Canada showing that hypofractionation (HF) radiotherapy is at least as favorable as normofractionation (NF) schemes for whole-breast irradiation (WBI) in terms of loco-regional control and cosmetic outcome, some radiation oncologists are reluctant to use HF WBI fearing increased toxicity, especially in large breasted patients. In this study the effect of the fractionation schedule on acute toxicity was investigated in a cohort of 229 breast cancer patients with various cup sizes treated with WBI in 2 different radiotherapy centers. Methods: From May 2010 till December 2012, 150 patients from Ghent University Hospital (GUH) and 79 patients from Clinique et Maternite Sainte-Elisabeth Namur (CMSE) were included in a prospective study aiming at developing a prediction model for radiation-related breast toxicity using clinical, dosimetric and genetic parameters. All patients at GUH were treated with a HF scheme of 40,05 Gy in 15 fractions. At CMSE patients with a cup size D or more were treated with NF WBI (50 Gy in 25 fractions), while patients with a cup size Results: Patients with a cup size Conclusions: HF whole-breast radiotherapy results in significantly less moist desquamation compared to NF regardless of cup size. Disclosure: All authors have declared no conflicts of interest.