1 The dosimetric impact of intra-fraction breath hold variations during mono-isocentric left breast irradiation including nodal regions. 'A diamond with a flaw is worth more than a pebble without imperfections' Radiotherapy department CHU UCL Namur Site Clinique Sainte Elisabeth, Namur and Centre Hospitalier Mouscron AMPR, Association Meuse Picarde de Radiothérapie Ann Van Esch, Martijn Swimberghe, Khalil Mahjoubi, Francois Sergent and Vincent Remouchamps Abstract The aim of this study is to investigate the safety of the mono-isocentric treatment technique using non-divergent field junctions in breast cancer patients while performing moderate Deep Inspiration Breath Hold. Data were obtained on a cohort of 18 patients. For these patients, the impact of variations in the level of the breath hold (and intra-fraction movement) was quantified through the retrospective 3D dose reconstruction of the actual treatment, taking into account the actual patient position during each treatment field and each treatment session. This real-life patient information was obtained through portal image analysis for every treatment field. Comparison of the thus reconstructed dose distribution to the theoretically envisioned dose distribution allows us to conclude that mono-isocentric breast treatments can be safely combined with moderate Deep Inspiration Breath Hold techniques. Background and Introduction
2 Nodal irradiation in breast cancer is highly debated nowadays and remains a challenging technical problem. Randomized data show the overall survival benefit of post-operative breast cancer irradiation including nodal regions [Ragaz 1997, Overgaard 1997]. Normal tissue toxicities, however, are not to be ignored and nodal irradiation remains a highly controversial topic in moderate risk patients [DARBY 2013]. In 2014, two large randomized studies and one large non-randomized prospective trial have highlighted the role of adjuvant nodal fields during post-operative locally advanced breast cancer irradiation, significantly improving long-term overall and disease-specific survival [Whelan 2015, Poortmans 2015, Thorsen 2016]. Moreover, international delineation consensus largely evolved in the recent months [Verhoeven 2015, Offersen 2015]. In addition, the development of technical solutions to irradiate the breast/chest wall and selected nodal regions with appropriate target coverage while assuring adequate protection of the organs at risk remains technically challenging. The use of half or quarter beams in a mono-isocentric field set up helps to solve the field junction issue. Full IMRT or VMAT solutions are actively studied but remain unconvincing due to unwanted dose contribution to the contra-lateral breast and lungs. Therefore, the simple mono-isocentric tangential field set up remains current practice in many centers. For heart sparing during left breast irradiation, planning studies showed the interest of moderate Deep Inspiration Breath Hold (mdibh) [Remouchamps 2003a]. Although a number of commercial solutions are available for respiratory monitoring or gating, we prefer a simple audio-guided breath hold technique, using nothing but the in-room camera's and the MV on-line portal imaging in continuous acquisition mode to monitor the chest wall during treatment. This simple technique has been shown to give very good results while being well supported by patients. Clinical implementation of mdibh was mostly reported for tangential breast/chest wall without nodal irradiation [Remouchamps 2003b; Korreman 2005]. When combining both the mono-isocentric treatment technique with breath hold, however, the accuracy with which the breath hold can be reproduced between consecutive fields has a potentially important impact on the field junction (possible gap or overlap). To our knowledge, no data can be found in the current literature on the practical accuracy of the combination of mono-isocentric and mdibh breast treatment. We have treated patients using the combination of mdibh and mono-isocentric treatment techniques using online portal imaging for positional verification. Based on the retrospective image analysis of these patients, we are able to report on the intra-fraction field junction accuracy between
3 the tangential and supraclavicular fields and to simulate the dosimetric impact of the measured deviations. Material & Methods Eighteen female patients with node-positive breast cancer were irradiated postoperatively during mdibh using a mono-isocentric three-field technique with theoretically and geometrically perfect field junctions, non-divergent at the isocenter located at the junction. All patients were positioned with both arms raised and supported using a dedicated inclined breast board (Breast Step, Elekta, Crawley) and had a computed tomography simulation using free breathing and mdibh. For the 18 patients in this analysis, mdibh was required to achieve satisfactory heart sparing [Ref VR]. Field positioning was defined by the placement of a single isocenter in the lung, 1-2 cm internally to the ribs at the level of the lower part of the clavicular head [De Meerleer 1997]. Asymmetric jaws were used to obtain non-divergent field edges [De Meerler 1997] to ensure a theoretically perfect junction of the opposed tangential breast fields (quarter fields, caudally) with the supraclavicular and axillar anterior oblique fields (half-fields cranially) (figure 1a). All patients were treated on a conventional photon linear accelerator (Clinac 2100C/21EX, Varian Medical System, Palo Alto) using a millennium MLC and amorphous silicon portal imager as1000. The dosimetric calculations were performed on the Eclipse treatment planning system using the AAA algorithm (version 11.0.31) (Varian Medical System, Palo Alto). Dose homogeneity within the breast CTV was optimized using the irregular surface compensator modules to create a dynamic MLC, a simple form of Intensity Modulated Radiotherapy (IMRT) on the two opposed tangential fields. The field apertures were adapted to the contoured nodal structures (supraclavicular and axillary level III in all cases, axillary level II, level I and internal mammary region depending upon the physician decision). The breast and/or chest wall were outlined clinically with radio-opaque wires placed on the patient's skin during the CT simulation as a definition of minimal field borders. The treatment-approved plans aimed to cover at least 95 % of the clinical target volume by at least 95 % of the prescribed dose for the breast/chest wall, but an underdosage was accepted in the nodal regions as the contouring was retrospectively corrected based on the more recent ESTRO consensus (figure 1b.) (ref OFFERSEN and Verhoeven ESTRO 2014). No PTV margin was used at that time, due to the in-progress CTV consensus and clinically sufficient target coverage. The tangential fields include a skin flash of 2-3 cm.
4 a. b. Figure 1: a. Mono-isocentric setup for breast treatment including nodal irradiation: opposed tangential breast fields (quarter fields, caudally) with the supraclavicular and axillar anterior oblique fields (half-fields cranially). The magenta 'Field junction' volume is defined as the 3D portion of the 50% isodose volume (indicated by the light yellow structure) in the planes within 1 cm of the junction, both in cranial and caudal direction. b. The anatomically outlined structures (red: breast CTV, cyan: subclavicular nodes, dark blue: axillary nodes, yellow: brachial plexus) as well as the artificial 'field junction' structure After positioning the patient on the treatment unit based on the skin marks during breath hold, portal images of the tangential and supraclavicular fields were acquired before treatment delivery to assure adequate patient set up during every treatment session. During treatment, continuous image acquisition was used as a visual feedback on the stability of the patient's breath hold. The acquired images were retrospectively analyzed: based on the matching results between the portal images and the Digitally Reconstructed Radiographs (DRR), the patient position (including the effect of each individual breath hold) could be determined for every field and for every treatment session. These actual positions were used to retrospectively reconstruct the delivered dose for every treatment session. The total 3D dose was obtained by summing up the dose reconstructions over all sessions. (figure 2)
5 Figure 2: Total dose distribution assuming the theoretically perfect isocentre position (left) and the reconstructed dose distribution based on the field-by-field, session-by-session analysis of the patient's true position as measured by the portal imager (right). To allow us to zoom in on the impact of positioning and consecutive breath hold uncertainties in the area around the field junction, a 'field junction' volume was generated on the patient CT. This volume was defined as the area encompassed by the 50% isodose of the original, theoretical 3D dose in the slices around the field junction (up to 1 cm above and below the field junction, as shown in figure 1). In addition, the dosimetric quality of the reconstructed plan was assessed by means of dose volume histograms (DVH) of those anatomical structures that could be affected by reduced dose homogeneity in the area of the field junction, i.e. breast and nodal CTV and brachial plexus. (The brachial plexus being difficult to delineate was defined with sufficient margins to ensure an analysis on the safe side.) These real-life reconstructed DVHs were compared to the original plan in which a perfect isocenter position was assumed. Results Comparison of the dose volume histograms shows mainly three categories of patients. A typical example for each category is shown in figure 3. For more than half of the patients (10 out of 18) (figure 3a), no significant difference is observed between the theoretical and the reconstructed DVH, not even at the level of the field junction. For these patients, small imprecisions in positioning (or breath hold reproducibility) appear random and average out over the whole treatment. A second, smaller category (6 out of 18 patients) shows a moderate difference between the theoretical and
6 reconstructed DVHs (figure 3b). For 2 out of 18 patients, the DVH of the practical reconstruction diverges markedly from the theoretical DVH, the difference being most pronounced at the level of the field junction (and axillary nodes) for which an overdosage is observed (figure 3c). Figure 3: Typical examples of theoretically expected (solid lines) and real-life reconstructed (dashed lines) DVH for the three categories of patients: a. 10/18 patients show no significant difference whatsoever, b. 6/18 show reduced dose homogeneity in the nodes, also accompanied by a lower dose at the level of the field junction, c. 2/18 patients show an increased maximum dose at the level of the field junction and therefore also in the nodes that are situated in this anatomical area. The boxplots in figure 4 represent a graphical summary of the analysis of the dosimetric parameters for the outlined structures.
7 The data on the breast CTV firstly confirm that even in the theoretical plan, 95% of the target volume is not covered by the 95% isodose line. This is due to the previously mentioned retrospective corrections to the CTV based on the ESTRO recommendations while the treatment plan was optimized based on the radio-opaque markers placed during CT simulation. The positional variations during the different treatment sessions result in a lowering of the median dose and in a larger spread. However, all reconstructed treatments were found to result in clinically acceptable target coverage when submitted to a slice-by-slice visual inspection of the isodoses. The changes observed in the box plots relate to two areas in the patient: if changes in isodoses are observed, they are either located in the area of the cranio-caudal field junction or at the level of the thoracic wall. The most distinct lowering of the overall dose coverage is observed for the subclavicular nodes when the nodal volume extends into the area of the field junction. No changes in the dose to the brachial plexus were observed. As expected, the most prominent changes are observed in the artificial 'Field Junction' structure generated especially for the purpose of zooming in on the junction. The box plot displays the changes to the maximum dose in this area of concern. Within our cohort of patients, the median value of the maximum dose has not undergone any relevant changes. This is in agreement with the general observation on the DVHs: for the majority of the patients: no noteworthy changes are observed in the reconstructed DVH. However, the small increase in the spread around the median value is caused by the second category of patients for which a moderate widening in the DVH of the Field Junction was observed. The point marked as outlier (24) corresponds to the hot spot exceeding 70Gy as observed in one of two patients in the third category, characterized by a substantial overdosage in the reconstructed plan. The increase in the size of the upper whisker is due to the overdosage observed in the second patient of this category.
8 a. b. c. d. Figure 4: Boxplots summarizing the impact of the (inter- and) intrafraction positional variations on the CTV breast (a) and nodal CTV (b) dose coverage (V95), on the maximum dose (D2) to the plexus brachialis (c) and on the artificial field junction volume (d). Discussion The above real-live dose reconstructions provide reassuring data on the safety of combining the mono-isocentric and breath hold techniques. Although imperfections in the field junction due to imprecisions in the breath hold reproducibility (or due to intra-fraction movement) are unavoidable, for the majority of the patients (16/18), they appear to have no clinically relevant impact on neither the target coverage, nor on the organs at risk or the area of the field junction. For the two patients that retrospectively showed considerable DVH distortion in the Field Junction volume, an additional comparison was made with the older technique, leaving a gap between the supraclavicular and tangential fields (figure 5). As expected, the dose coverage obtained with the older technique at the level of the junction is vastly inferior to the mono-isocentric reconstructed plan, in spite of the
9 overdosage observed in the latter. In addition, no serious clinical symptoms were observed that can be attributed to the overdosage. Figure 5: Comparison of the traditional, non-mono-isocentric breast treatment (with imperfect field junction by definition) (dotted lines) to the theoretical (solid lines) and the reconstructed (dashed lines) mono-isocentric treatment for a patients for which the reconstructed dose of the monoisocentric treatment shows an overdosage in the field junction area. Conclusion Mono-isocentric treatments with non-divergent field junctions for loco-regional breast irradiation can be safely combined with moderate Deep Inspiration Breath Hold techniques. For the vast majority of the patients, small imperfections in the patient setup and breath hold reproducibility average out over the whole treatment and no significant hot or cold spots are observed at the level of the field junction. For the few patients for which the junction becomes dosimetrically suboptimal, the mono-isocentric treatment is still largely preferable over the older, non-isocentric technique with imperfect junctions by definition. References: [Ragaz 1997] 'Adjuvant Radiotherapy and Chemotherapy in Node-Positive Premenopausal Women with Breast Cancer' J Ragaz, S M. Jackson, N Le, I H Plenderleith, J J Spinelli, V E Basco, K S Wilson, M
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