- Email: [email protected]
Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy
Medical Dosimetry 40 (2015) 352–354
Medical Dosimetry journal homepage: www.meddos.org
Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy Henal Patel, B.A.,* Sharad Goyal, M.D.,y and Leonard Kim, M.S., A.Mus.D., D.A.B.R.y Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, NJ; and yRadiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, NJ
n
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 October 2014 Received in revised form 16 February 2015 Accepted 27 April 2015
Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end of whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT. & 2015 American Association of Medical Dosimetrists.
Keywords: Breast boost radiotherapy Boost target volume Resimulation Hydrogel fiducial markers
Introduction The observation that the lumpectomy cavity shrinks over time has led to recommendations that patients undergoing whole-breast radiotherapy be resimulated for boost planning.1-7 For a conformal boost, the target is often defined as the cavity plus a fixed margin. Thus, resimulation implicitly assumes that at-risk tissue near the cavity follows the cavity as it shrinks. In this case study, this assumption is called into question by a patient in whom injectable, hydrogel fiducial markers were placed in the tissue surrounding the cavity.
Case Description A 43-year-old woman palpated a mass in her left breast that was described on subsequent mammography as a nodular density measuring 1.3 0.9 1.2 cm3 in the upper outer quadrant of the breast. A biopsy of the primary tumor and axillary lymph node Reprint requests to Leonard Kim, Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, Room 2013, 195 Little Albany St, New Brunswick, NJ 08901. E-mail: [email protected] http://dx.doi.org/10.1016/j.meddos.2015.04.007 0958-3947/Copyright Ó 2015 American Association of Medical Dosimetrists
revealed invasive ductal carcinoma (high grade, þ lymphovascular invasion, and triple negative). She was categorized as having cT2N2M0 left breast cancer. She received neoadjuvant chemotherapy (Adriamycin and Cytoxan 4 and Taxol 8). After suboptimal response, carboplatin was added to the chemotherapy regimen and induced a near-complete response. She underwent left breast lumpectomy with axillary lymph node dissection during which 5 surgical clips were placed to mark the walls of the lumpectomy cavity. Final pathology revealed multifocal invasive ductal carcinoma with 1/6 lymph nodes positive for metastatic disease. She was seen for consultation by the radiation oncology team and was recommended comprehensive breast and nodal irradiation using conventional fractionation. At the time of initial simulation for radiotherapy planning, a radiation oncologist injected 4 aliquots of TraceIT Tissue Marker (Augmenix, Inc., Waltham, MA) each measuring 0.25 mL using a syringe and a 25-gauge needle supplied by the manufacturer. Guided by a preinjection scan, the markers were placed at locations 1.4 to 2.7 cm from the seroma, demarcating a volume similar to a 3-dimensional conformal boost PTV. The thin needle allowed the patient to tolerate the injection with minimal to no discomfort. The TraceIT Tissue Marker is a Food and Drug
H. Patel et al. / Medical Dosimetry 40 (2015) 352–354
353
Fig. 1. Radiopaque hydrogel markers in the breast as seen in CT and CBCT. CBCT, cone-beam computed tomography.
Administration–approved, injectable synthetic hydrogel composed of water and iodinated, cross-linked polyethylene glycol. The fluid polymerizes upon injection, forming a well-localized bleb within tissue. In cadaveric studies, the marker showed excellent visibility in the thorax in multiple common imaging modalities such as CT, cone-beam CT, magnetic resonance imaging, and ultrasound.8 The marker is absorbed slowly by the body over a period of 3 months, offering applications as a non-permanent marker. Corresponding views in CT and cone-beam computed tomography of 2 fiducials placed in breast tissue are shown in Fig. 1. The patient was treated to the left breast and regional nodes using a 3-field monoisocentric technique. The breast and nodes received doses of 5000 and 4600 cGy, respectively, in 200-cGy fractions. This was followed by a 3-dimensional conformal cavity boost dose of 1000 cGy in 200-cGy fractions. The patient tolerated treatment very well with minimal side effects. In the initial planning CT, the seroma volume was 18 cm3. A new CT for boost planning was acquired 4.5 weeks into radiation therapy in which the seroma volume had shrunk to 7 cm3. Registration of the 2 images showed that the seroma and surgical clips had asymmetrically contracted inward. In contrast, the positions of hydrogel markers outside the seroma were relatively stable between the 2 scans (Fig. 2). Distances between pairs of surgical clips (1 to 3 cm apart) at the surgical bed boundary decreased by an average of 7 mm (standard deviation: 3 mm) between initial and boost simulation. In contrast, distances between pairs of hydrogel markers (5 to 10 cm apart) in the tissue surrounding the surgical bed decreased by an average of 3 mm (standard deviation: 1 mm) between initial and boost simulation. Therefore, for this patient, the decision was made to use the initial CT instead of the new CT for boost planning. Despite the reduced seroma volume in the later CT, it was felt that a similarly reduced at-risk tissue volume could not be inferred. Breast tissue is elastically compressible,9 which may explain the observed result. However, even without consideration of the elastic nature of breast tissue, this result may not be unexpected. If one wishes to preserve the volume of at-risk tissue targeted by the boost, then the outer margin of the target volume cannot shrink as quickly as the inner cavity does. For example, in a simple geometric model where the target and cavity consist of 2 concentric spheres of radii measuring 3.0 and 1.5 cm, respectively, if the cavity's volume shrinks to half, the inner radius reduces by 3.1 mm, but the outer target radius reduces by only 0.6 mm.
Conclusions We injected hydrogel fiducial markers in breast tissue near the lumpectomy cavity of a patient undergoing whole-breast radiotherapy. CT scans acquired at the beginning and end of wholebreast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by the gel markers, leading us to use the initial planning CT for boost planning. The information gained from the extra hydrogel markers at the target margins (rather than the cavity walls) calls into question the usual interpretation of cavity shrinkage for boost target definition and warrants further study.
Acknowledgment The markers used in this case study were provided for evaluation purposes by the manufacturer, Augmenix, Inc.
Fig. 2. Surgical clip and gel marker positions in 2 scans acquired 4.5 weeks apart. The surgical clips (first scan: red; second scan: blue) moved between the 2 scans, tracking the shrinkage of the lumpectomy cavity. In contrast, the positions of gel markers (first scan: green; second scan: magenta) placed outside the seroma were relatively stable.
354
H. Patel et al. / Medical Dosimetry 40 (2015) 352–354
References 1. Jacobson, G.; Betts, V.; Smith, B. Change in volume of lumpectomy cavity during external-beam irradiation of the intact breast. Int. J. Radiat. Oncol. Biol. Phys. 65:1161–4; 2006. 2. Prendergast, B.; Indelicato, D.J.; Grobmeyer, S.R.; et al. The dynamic tumor bed: Volumetric changes in the lumpectomy cavity during breast-conserving therapy. Int. J. Radiat. Oncol. Biol. Phys. 74:695–701; 2009. 3. Hepel, J.T.; Evans, S.B.; Hiatt, J.R.; et al. Planning the breast boost: Comparison of three techniques and evolution of tumor bed during treatment. Int. J. Radiat. Oncol. Biol. Phys. 74:758–63; 2009. 4. Tersteeg, R.J.H.A.; Roesink, J.M.; Albregts, M.; et al. Changes in excision cavity volume: prediction of the reduction in absolute volume during breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 74:1181–5; 2009.
5. Sharma, R.; Spierer, M.; Mutyala, S.; et al. Change in seroma volume during whole-breast radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 75:89–93; 2009. 6. Flannery, T.W.; Nichols, E.M.; Cheston, S.B.; et al. Repeat computed tomography simulation to assess lumpectomy cavity volume during whole-breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 75:751–6; 2009. 7. Truong, M.T.; Hirsch, A.E.; Kovalchuk, N.; et al. Cone-beam computed tomography image guided therapy to evaluate lumpectomy cavity variation before and during breast radiotherapy. J. Appl. Clin. Med. Phys. 14:209–19; 2013. 8. de Souza, L.L.; Ford, E.; Gilbert, C.; et al. Novel applications of an injectable radiopaque hydrogel tissue marker for management of thoracic malignancies. Chest 143:1635–41; 2013. 9. Price, B.D.; Gibson, A.P.; Tan, L.T.; et al. An elastically compressible phantom material with mechanical and x-ray attenuation properties equivalent to breast tissue. Phys. Med. Biol. 55:1177–88; 2010.
Medical Dosimetry journal homepage: www.meddos.org
Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy Henal Patel, B.A.,* Sharad Goyal, M.D.,y and Leonard Kim, M.S., A.Mus.D., D.A.B.R.y Rutgers Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, NJ; and yRadiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, New Brunswick, NJ
n
A R T I C L E I N F O
A B S T R A C T
Article history: Received 2 October 2014 Received in revised form 16 February 2015 Accepted 27 April 2015
Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end of whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT. & 2015 American Association of Medical Dosimetrists.
Keywords: Breast boost radiotherapy Boost target volume Resimulation Hydrogel fiducial markers
Introduction The observation that the lumpectomy cavity shrinks over time has led to recommendations that patients undergoing whole-breast radiotherapy be resimulated for boost planning.1-7 For a conformal boost, the target is often defined as the cavity plus a fixed margin. Thus, resimulation implicitly assumes that at-risk tissue near the cavity follows the cavity as it shrinks. In this case study, this assumption is called into question by a patient in whom injectable, hydrogel fiducial markers were placed in the tissue surrounding the cavity.
Case Description A 43-year-old woman palpated a mass in her left breast that was described on subsequent mammography as a nodular density measuring 1.3 0.9 1.2 cm3 in the upper outer quadrant of the breast. A biopsy of the primary tumor and axillary lymph node Reprint requests to Leonard Kim, Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, the State University of New Jersey, Room 2013, 195 Little Albany St, New Brunswick, NJ 08901. E-mail: [email protected] http://dx.doi.org/10.1016/j.meddos.2015.04.007 0958-3947/Copyright Ó 2015 American Association of Medical Dosimetrists
revealed invasive ductal carcinoma (high grade, þ lymphovascular invasion, and triple negative). She was categorized as having cT2N2M0 left breast cancer. She received neoadjuvant chemotherapy (Adriamycin and Cytoxan 4 and Taxol 8). After suboptimal response, carboplatin was added to the chemotherapy regimen and induced a near-complete response. She underwent left breast lumpectomy with axillary lymph node dissection during which 5 surgical clips were placed to mark the walls of the lumpectomy cavity. Final pathology revealed multifocal invasive ductal carcinoma with 1/6 lymph nodes positive for metastatic disease. She was seen for consultation by the radiation oncology team and was recommended comprehensive breast and nodal irradiation using conventional fractionation. At the time of initial simulation for radiotherapy planning, a radiation oncologist injected 4 aliquots of TraceIT Tissue Marker (Augmenix, Inc., Waltham, MA) each measuring 0.25 mL using a syringe and a 25-gauge needle supplied by the manufacturer. Guided by a preinjection scan, the markers were placed at locations 1.4 to 2.7 cm from the seroma, demarcating a volume similar to a 3-dimensional conformal boost PTV. The thin needle allowed the patient to tolerate the injection with minimal to no discomfort. The TraceIT Tissue Marker is a Food and Drug
H. Patel et al. / Medical Dosimetry 40 (2015) 352–354
353
Fig. 1. Radiopaque hydrogel markers in the breast as seen in CT and CBCT. CBCT, cone-beam computed tomography.
Administration–approved, injectable synthetic hydrogel composed of water and iodinated, cross-linked polyethylene glycol. The fluid polymerizes upon injection, forming a well-localized bleb within tissue. In cadaveric studies, the marker showed excellent visibility in the thorax in multiple common imaging modalities such as CT, cone-beam CT, magnetic resonance imaging, and ultrasound.8 The marker is absorbed slowly by the body over a period of 3 months, offering applications as a non-permanent marker. Corresponding views in CT and cone-beam computed tomography of 2 fiducials placed in breast tissue are shown in Fig. 1. The patient was treated to the left breast and regional nodes using a 3-field monoisocentric technique. The breast and nodes received doses of 5000 and 4600 cGy, respectively, in 200-cGy fractions. This was followed by a 3-dimensional conformal cavity boost dose of 1000 cGy in 200-cGy fractions. The patient tolerated treatment very well with minimal side effects. In the initial planning CT, the seroma volume was 18 cm3. A new CT for boost planning was acquired 4.5 weeks into radiation therapy in which the seroma volume had shrunk to 7 cm3. Registration of the 2 images showed that the seroma and surgical clips had asymmetrically contracted inward. In contrast, the positions of hydrogel markers outside the seroma were relatively stable between the 2 scans (Fig. 2). Distances between pairs of surgical clips (1 to 3 cm apart) at the surgical bed boundary decreased by an average of 7 mm (standard deviation: 3 mm) between initial and boost simulation. In contrast, distances between pairs of hydrogel markers (5 to 10 cm apart) in the tissue surrounding the surgical bed decreased by an average of 3 mm (standard deviation: 1 mm) between initial and boost simulation. Therefore, for this patient, the decision was made to use the initial CT instead of the new CT for boost planning. Despite the reduced seroma volume in the later CT, it was felt that a similarly reduced at-risk tissue volume could not be inferred. Breast tissue is elastically compressible,9 which may explain the observed result. However, even without consideration of the elastic nature of breast tissue, this result may not be unexpected. If one wishes to preserve the volume of at-risk tissue targeted by the boost, then the outer margin of the target volume cannot shrink as quickly as the inner cavity does. For example, in a simple geometric model where the target and cavity consist of 2 concentric spheres of radii measuring 3.0 and 1.5 cm, respectively, if the cavity's volume shrinks to half, the inner radius reduces by 3.1 mm, but the outer target radius reduces by only 0.6 mm.
Conclusions We injected hydrogel fiducial markers in breast tissue near the lumpectomy cavity of a patient undergoing whole-breast radiotherapy. CT scans acquired at the beginning and end of wholebreast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by the gel markers, leading us to use the initial planning CT for boost planning. The information gained from the extra hydrogel markers at the target margins (rather than the cavity walls) calls into question the usual interpretation of cavity shrinkage for boost target definition and warrants further study.
Acknowledgment The markers used in this case study were provided for evaluation purposes by the manufacturer, Augmenix, Inc.
Fig. 2. Surgical clip and gel marker positions in 2 scans acquired 4.5 weeks apart. The surgical clips (first scan: red; second scan: blue) moved between the 2 scans, tracking the shrinkage of the lumpectomy cavity. In contrast, the positions of gel markers (first scan: green; second scan: magenta) placed outside the seroma were relatively stable.
354
H. Patel et al. / Medical Dosimetry 40 (2015) 352–354
References 1. Jacobson, G.; Betts, V.; Smith, B. Change in volume of lumpectomy cavity during external-beam irradiation of the intact breast. Int. J. Radiat. Oncol. Biol. Phys. 65:1161–4; 2006. 2. Prendergast, B.; Indelicato, D.J.; Grobmeyer, S.R.; et al. The dynamic tumor bed: Volumetric changes in the lumpectomy cavity during breast-conserving therapy. Int. J. Radiat. Oncol. Biol. Phys. 74:695–701; 2009. 3. Hepel, J.T.; Evans, S.B.; Hiatt, J.R.; et al. Planning the breast boost: Comparison of three techniques and evolution of tumor bed during treatment. Int. J. Radiat. Oncol. Biol. Phys. 74:758–63; 2009. 4. Tersteeg, R.J.H.A.; Roesink, J.M.; Albregts, M.; et al. Changes in excision cavity volume: prediction of the reduction in absolute volume during breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 74:1181–5; 2009.
5. Sharma, R.; Spierer, M.; Mutyala, S.; et al. Change in seroma volume during whole-breast radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 75:89–93; 2009. 6. Flannery, T.W.; Nichols, E.M.; Cheston, S.B.; et al. Repeat computed tomography simulation to assess lumpectomy cavity volume during whole-breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 75:751–6; 2009. 7. Truong, M.T.; Hirsch, A.E.; Kovalchuk, N.; et al. Cone-beam computed tomography image guided therapy to evaluate lumpectomy cavity variation before and during breast radiotherapy. J. Appl. Clin. Med. Phys. 14:209–19; 2013. 8. de Souza, L.L.; Ford, E.; Gilbert, C.; et al. Novel applications of an injectable radiopaque hydrogel tissue marker for management of thoracic malignancies. Chest 143:1635–41; 2013. 9. Price, B.D.; Gibson, A.P.; Tan, L.T.; et al. An elastically compressible phantom material with mechanical and x-ray attenuation properties equivalent to breast tissue. Phys. Med. Biol. 55:1177–88; 2010.