Clinical Oncology 26 (2014) 677e683 Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Original Article
Estimating the Value of Surgical Clips for Target Volume Delineation in External Beam Partial Breast Radiotherapy E. Ippolito *, L. Trodella *, S. Silipigni *, R.M. D’Angelillo *, A. Di Donato *, M. Fiore *, A. Grasso y, E. Angelini y, S. Ramella *, V. Altomare y * Radiation y
Oncology, Campus Bio-Medico University, Rome, Italy Department of Senology, Campus Bio-Medico University, Rome, Italy
Received 9 September 2013; received in revised form 15 July 2014; accepted 21 July 2014
Abstract Aims: To investigate the role of surgical clips in defining the clinical target volume (CTV) for three-dimensional conformal external beam radiotherapy-partial breast irradiation (3D-CRT-PBI) using preoperative computed tomography scans. Materials and methods: A group of patients with early breast cancer underwent conservative surgery with placement of surgical titanium clips (at least three clips required). All patients had a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were coregistered with a match point registration. The relationship between the clips-based CTV for PBI delineated on CT2 and the initial tumour location on CT1 was studied, evaluating the percentage of intersection volume. Results: Twenty-eight patients participated in this study. In total, 13 patients (46.4%) had an intersection volume 50% and 10 patients (35.7%) had complete intersection (intersection volume ¼ 100%). An increased median intersection volume was observed in patients with more than six clips (P ¼ 0.007) and in patients with a larger portion of breast volume covered by the PBI-CTV (CTV/BV; P ¼ 0.010). Intersection volume increased with the number of clips, after adjustment for CTV/BV (linear coefficient ¼ 5.1693; P ¼ 0.043). Also, a maximum distance from the chest wall 0.7 cm and CTV/BV > 9.5% were found to be predictors of an intersection volume 50% (area under the curve 0.841; confidence interval 0.649e0.952; P < 0.0001; area under the curve 0.800; confidence interval 0.607e0.926; P ¼ 0.0004) and of an intersection volume of 100% (area under the curve 0.776, confidence interval 0.573e0.916, P ¼ 0.046; area under the curve 0.752, confidence interval 0.536e0.935; P ¼ 0.032). Conclusions: Titanium clips are essential and six or more increase the accuracy of tumour bed delineation for PBI; also the primary tumour location as well as the percentage of volume of breast covered by PBI-CTV may influence the correct delineation of PBI-CTV. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Key words: Partial breast irradiation; surgical clips
Introduction Accelerated partial breast irradiation (APBI) is an emerging radiation treatment modality that allows the overall treatment time, commitment and cost of breast radiotherapy to be reduced. The rationale for using APBI stems from pathological data on patterns of recurrence, which had shown that 90% of recurrent disease occurs in the breast within the index Author for correspondence: E. Ippolito, Radiation Oncology, Campus BioMedico University, Rome, Italy. Tel: þ39-06-22541419; Fax: þ39-0622541433. E-mail address: [email protected] (E. Ippolito).
quadrant and that the incidence of new tumours in the ipsilateral breast remote from the original index is comparable with that documented in the contralateral breast [1e4]. As such, APBI may achieve an adequate local control rate targeting the location of the primary tumour with a limited margin of normal tissue, and it is currently under evaluation in several phase III studies as an alternative to whole breast irradiation for the adjuvant treatment of selected groups of patients with early breast cancer [5e12]. Different technical modalities, including interstitial brachytherapy, balloon catheter brachytherapy, intraoperative radiotherapy and three-dimensional conformal external beam radiotherapy (3D-CRT) have been explored to deliver APBI. Overall, brachytherapy-based techniques
http://dx.doi.org/10.1016/j.clon.2014.08.003 0936-6555/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
678
E. Ippolito et al. / Clinical Oncology 26 (2014) 677e683
have provided the largest group of patients with the longest follow-up period [13,14]. However, these techniques require experience and adequately skilled operators and are not available in all radiotherapy units. Based on these recognised issues there is great interest in examining the use of 3D-CRT to deliver APBI. Even if 3D-CRT is largely available and easy to use, there are some issues and unanswered questions to address when this technique is used to deliver APBI. These include breathing motion and treatment set-up variation, which may lead to the adoption of a larger planning target volume. Furthermore, the identification and contouring of the tumour bed can be crucial, as in 3D-CRT-PBI the clinical target volume (CTV) cannot be directly visualised. Tumour bed identification usually uses a combination of factors, including the initial location of the tumour base on radiology studies, the site of visible seroma on computed tomography and breast distortion after surgery. Studies evaluating the accuracy of the definition of tumour bed boost have shown that contouring can vary among operators and that geographical misses are frequent [15,16]. Surgical clips are recommended to accurately delineate the surgical cavity as postoperative anatomy on computed tomography scans may be quite different from the preoperative one [17]. In whole breast radiotherapy with or without tumour bed boost, surgical clips can guide tangential beam arrangements for adequate coverage of the tumour bed [18]. They are also essential for simultaneous integrated boost radiotherapy as they may enable the use of smaller planning target volumes, reducing the risk of late normal tissue toxicity [19]. In this study we investigated the role of surgical clips in defining the tumour bed, evaluating the relationship between the clips-based CTV for APBI and the initial tumour location evaluated on a preoperative computed tomography scan.
Materials and Methods A group of patients with early breast cancer (cT1-T2, N0eN1, M0), candidates for conservative surgery, were entered into this study. All patients underwent conservative surgery with sentinel lymph node biopsy and/or lymph node dissection with placement of surgical titanium clips (fixed to the pectoralis major fascia and others placed on each side of the surgical cavity). A minimum of three surgical clips was required. The number of clips used for each patient depended on surgeon choice and was not related to tumour size. After tumour excision and clips placement, breast tissue remodelling with full thickness closure of the lumpectomy cavity was carried out. These patients underwent a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were co-registered with a match point registration. Patients were immobilised in the supine position with an Accufix Breast Board device. A simulation computed tomography scan was
obtained at 3 mm intervals. Two different physicians delineated volumes on CT1 and CT2 so as not to be influenced in defining PBI-CTV volume by knowing the location of the primary tumour. The breast volume was delineated according to the Radiation Therapy Oncology Group (RTOG) Breast Cancer Atlas on both CT1 and CT2. The gross tumour volume (GTV) was delineated on CT1 as the visible tumour: the PBI-CTV was defined on CT2 by the surgical clips with a uniform 15 mm margin [8], limited to 4 mm from the skin surface and chest wall (major pectoralis fascia). Statistical Analysis The number of clips for each patient was recorded. The maximum distance from the centre of the GTV to either the chest wall (MD-CW) or the skin (MD-S), the GTV (cm3), the PBI-CTV (cm3), the ratio of PBI-CTV to ipsilateral breast volume (CTV/BV) and breast volume (cm3) on both CT1 (BCT1) and CT2 (BCT2) were calculated for each patient. An intersection volume, defined as the percentage ratio between the intersection of the contoured GTV and PBI-CTV (intersection volume/GTV 100) (Figure 1) was computed for each patient. Normality was tested using the ShapiroeWilk test. Patients were divided in two groups according to the number of clips: patients with fewer than six clips, patients with six or more clips. We chose the number of six clips as the cut-off point as this is the number of clips recommended in most recent studies [20]. The ManneWhitney test was used to compare the intersection volume between these two groups. A linear regression analysis was also carried out to evaluate the relationship between intersection volume and the number of clips and CTV/BV was considered as continuous covariates. The variance inflation factor was calculated to quantify the severity of the multicollinearity in the regression analysis. Furthermore, patients were divided on the basis of the intersection volume into patients with an intersection volume
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Original Article
Estimating the Value of Surgical Clips for Target Volume Delineation in External Beam Partial Breast Radiotherapy E. Ippolito *, L. Trodella *, S. Silipigni *, R.M. D’Angelillo *, A. Di Donato *, M. Fiore *, A. Grasso y, E. Angelini y, S. Ramella *, V. Altomare y * Radiation y
Oncology, Campus Bio-Medico University, Rome, Italy Department of Senology, Campus Bio-Medico University, Rome, Italy
Received 9 September 2013; received in revised form 15 July 2014; accepted 21 July 2014
Abstract Aims: To investigate the role of surgical clips in defining the clinical target volume (CTV) for three-dimensional conformal external beam radiotherapy-partial breast irradiation (3D-CRT-PBI) using preoperative computed tomography scans. Materials and methods: A group of patients with early breast cancer underwent conservative surgery with placement of surgical titanium clips (at least three clips required). All patients had a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were coregistered with a match point registration. The relationship between the clips-based CTV for PBI delineated on CT2 and the initial tumour location on CT1 was studied, evaluating the percentage of intersection volume. Results: Twenty-eight patients participated in this study. In total, 13 patients (46.4%) had an intersection volume 50% and 10 patients (35.7%) had complete intersection (intersection volume ¼ 100%). An increased median intersection volume was observed in patients with more than six clips (P ¼ 0.007) and in patients with a larger portion of breast volume covered by the PBI-CTV (CTV/BV; P ¼ 0.010). Intersection volume increased with the number of clips, after adjustment for CTV/BV (linear coefficient ¼ 5.1693; P ¼ 0.043). Also, a maximum distance from the chest wall 0.7 cm and CTV/BV > 9.5% were found to be predictors of an intersection volume 50% (area under the curve 0.841; confidence interval 0.649e0.952; P < 0.0001; area under the curve 0.800; confidence interval 0.607e0.926; P ¼ 0.0004) and of an intersection volume of 100% (area under the curve 0.776, confidence interval 0.573e0.916, P ¼ 0.046; area under the curve 0.752, confidence interval 0.536e0.935; P ¼ 0.032). Conclusions: Titanium clips are essential and six or more increase the accuracy of tumour bed delineation for PBI; also the primary tumour location as well as the percentage of volume of breast covered by PBI-CTV may influence the correct delineation of PBI-CTV. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Key words: Partial breast irradiation; surgical clips
Introduction Accelerated partial breast irradiation (APBI) is an emerging radiation treatment modality that allows the overall treatment time, commitment and cost of breast radiotherapy to be reduced. The rationale for using APBI stems from pathological data on patterns of recurrence, which had shown that 90% of recurrent disease occurs in the breast within the index Author for correspondence: E. Ippolito, Radiation Oncology, Campus BioMedico University, Rome, Italy. Tel: þ39-06-22541419; Fax: þ39-0622541433. E-mail address: [email protected] (E. Ippolito).
quadrant and that the incidence of new tumours in the ipsilateral breast remote from the original index is comparable with that documented in the contralateral breast [1e4]. As such, APBI may achieve an adequate local control rate targeting the location of the primary tumour with a limited margin of normal tissue, and it is currently under evaluation in several phase III studies as an alternative to whole breast irradiation for the adjuvant treatment of selected groups of patients with early breast cancer [5e12]. Different technical modalities, including interstitial brachytherapy, balloon catheter brachytherapy, intraoperative radiotherapy and three-dimensional conformal external beam radiotherapy (3D-CRT) have been explored to deliver APBI. Overall, brachytherapy-based techniques
http://dx.doi.org/10.1016/j.clon.2014.08.003 0936-6555/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
678
E. Ippolito et al. / Clinical Oncology 26 (2014) 677e683
have provided the largest group of patients with the longest follow-up period [13,14]. However, these techniques require experience and adequately skilled operators and are not available in all radiotherapy units. Based on these recognised issues there is great interest in examining the use of 3D-CRT to deliver APBI. Even if 3D-CRT is largely available and easy to use, there are some issues and unanswered questions to address when this technique is used to deliver APBI. These include breathing motion and treatment set-up variation, which may lead to the adoption of a larger planning target volume. Furthermore, the identification and contouring of the tumour bed can be crucial, as in 3D-CRT-PBI the clinical target volume (CTV) cannot be directly visualised. Tumour bed identification usually uses a combination of factors, including the initial location of the tumour base on radiology studies, the site of visible seroma on computed tomography and breast distortion after surgery. Studies evaluating the accuracy of the definition of tumour bed boost have shown that contouring can vary among operators and that geographical misses are frequent [15,16]. Surgical clips are recommended to accurately delineate the surgical cavity as postoperative anatomy on computed tomography scans may be quite different from the preoperative one [17]. In whole breast radiotherapy with or without tumour bed boost, surgical clips can guide tangential beam arrangements for adequate coverage of the tumour bed [18]. They are also essential for simultaneous integrated boost radiotherapy as they may enable the use of smaller planning target volumes, reducing the risk of late normal tissue toxicity [19]. In this study we investigated the role of surgical clips in defining the tumour bed, evaluating the relationship between the clips-based CTV for APBI and the initial tumour location evaluated on a preoperative computed tomography scan.
Materials and Methods A group of patients with early breast cancer (cT1-T2, N0eN1, M0), candidates for conservative surgery, were entered into this study. All patients underwent conservative surgery with sentinel lymph node biopsy and/or lymph node dissection with placement of surgical titanium clips (fixed to the pectoralis major fascia and others placed on each side of the surgical cavity). A minimum of three surgical clips was required. The number of clips used for each patient depended on surgeon choice and was not related to tumour size. After tumour excision and clips placement, breast tissue remodelling with full thickness closure of the lumpectomy cavity was carried out. These patients underwent a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were co-registered with a match point registration. Patients were immobilised in the supine position with an Accufix Breast Board device. A simulation computed tomography scan was
obtained at 3 mm intervals. Two different physicians delineated volumes on CT1 and CT2 so as not to be influenced in defining PBI-CTV volume by knowing the location of the primary tumour. The breast volume was delineated according to the Radiation Therapy Oncology Group (RTOG) Breast Cancer Atlas on both CT1 and CT2. The gross tumour volume (GTV) was delineated on CT1 as the visible tumour: the PBI-CTV was defined on CT2 by the surgical clips with a uniform 15 mm margin [8], limited to 4 mm from the skin surface and chest wall (major pectoralis fascia). Statistical Analysis The number of clips for each patient was recorded. The maximum distance from the centre of the GTV to either the chest wall (MD-CW) or the skin (MD-S), the GTV (cm3), the PBI-CTV (cm3), the ratio of PBI-CTV to ipsilateral breast volume (CTV/BV) and breast volume (cm3) on both CT1 (BCT1) and CT2 (BCT2) were calculated for each patient. An intersection volume, defined as the percentage ratio between the intersection of the contoured GTV and PBI-CTV (intersection volume/GTV 100) (Figure 1) was computed for each patient. Normality was tested using the ShapiroeWilk test. Patients were divided in two groups according to the number of clips: patients with fewer than six clips, patients with six or more clips. We chose the number of six clips as the cut-off point as this is the number of clips recommended in most recent studies [20]. The ManneWhitney test was used to compare the intersection volume between these two groups. A linear regression analysis was also carried out to evaluate the relationship between intersection volume and the number of clips and CTV/BV was considered as continuous covariates. The variance inflation factor was calculated to quantify the severity of the multicollinearity in the regression analysis. Furthermore, patients were divided on the basis of the intersection volume into patients with an intersection volume
