Localising the Tumour Bed in Breast Radiotherapy

Abstract

Accurate Boost Localisation is ImportantAfter complete microscopic resection of primary tumour in women with early breast cancer, most local tumour relapses present close to the primary tumour [[1]Mannino M. Yarnold J. Accelerated partial breast irradiation trials: diversity in rationale and design.Radiother Oncol. 2009; 91: 16-22Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. It is therefore important to ensure that the tumour bed lies well inside the treatment volume encompassed by tangential fields to the whole breast and subsequent tumour bed boost. The penalty for geographical miss is severe: four local tumour relapses cause, on average, one death from breast cancer [[2]Clarke M. Collins R. Darby S. et al.Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.Lancet. 2006; 366: 2087-2106Abstract Full Text Full Text PDF Scopus (3949) Google Scholar]. The optimal margin to add to the excision cavity for whole breast radiotherapy and the tumour bed boost remains controversial, but there is general agreement that the excision cavity itself must always lie inside the high dose envelope.Boost Localisation is Currently Inaccurate and the Tumour Bed Sometimes Lies Outside Whole Breast TangentsThe tumour beds of medially and laterally located tumours are particularly prone to under-dosage if surface landmarks are used as fiducial points for whole breast radiotherapy planning (see Fig. 1) [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar]. It is therefore justified to restate the obvious: accurate tumour bed localisation is essential even for planning whole breast radiotherapy.It has been known for a very long time that clinical planning of the tumour bed boost volume based on preoperative imaging, surgical note and breast scar position is very unreliable [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar]. Increasingly, the breast scar is often placed some distance from the tumour for wire-guided localisation biopsy or better cosmetic outcome. In addition, the practice of oncoplastic surgery, whereby breast tissue is repositioned following wide local excision to minimise the surgical deficit, is becoming standard of care [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. In this situation, the preoperative imaging often bears very little relationship to the final position of the tumour bed.X-ray computed tomography or ultrasound imaging can use seroma as a surrogate for the tumour bed position, but there are limitations. First, the seroma is only clearly defined in around one-quarter of patients [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Second, the seroma underestimates the true extent of the tumour bed defined by implanted clips [[12]Coles C.E. Cash C.J. Treece G.M. et al.High definition three-dimensional ultrasound to localise the tumour bed: a breast radiotherapy planning study.Radiother Oncol. 2007; 84: 233-241Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]. In spectacular images collected by magnetic resonance, concentric rings of granulation tissue laid down in the wall of the excision cavity reduce the volume of seroma [[13]Whipp E.C. Halliwell M. Magnetic resonance imaging appearances in the postoperative breast: the clinical target volume-tumor and its relationship to the chest wall.Int J Radiat Oncol Biol Phys. 2008; 72: 49-57Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. This explains why the seroma is not a surrogate for the surgical cavity.Increasing the Margins is Not the AnswerUncertainty in localising the tumour bed in patients with medial or lateral tumours can be overcome by increasing the posterior field borders of whole breast tangents, but only at the expense of increased morbidity in the ribcage and lung, and potential mortality in women with left-sided tumours. The heart is the most sensitive organ, a few Gray being associated with increased risk of fatal heart disease, and every effort needs to be made to exclude the organ from the treatment volume [[14]Darby S.C. McGale P. Taylor C.W. Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries.Lancet Oncol. 2005; 6: 557-565Abstract Full Text Full Text PDF PubMed Scopus (787) Google Scholar]. When localising the tumour bed boost, increasing the clinical target volume is a crude way of avoiding geographical miss. This is particularly important in the emerging era of oncoplastic surgery, when the tumour bed may be well away from its primary location.Clips are the Obvious SolutionAn audit of the use of tumour bed clips vs standard anatomical landmarks for whole breast radiotherapy showed that the addition of clips modified the field borders in 43% (13/30) of cases [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Numerous studies have shown the greater accuracy of titanium clips in tumour bed boost radiotherapy planning compared with clinical mark up [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar, 15Bates A.T. Swift C.L. Kwa W. Moravan V. Aquino-Parsons C. A computed tomography-based protocol vs conventional clinical mark-up for breast electron boost.Clin Oncol (R Coll Radiol). 2007; 19: 349-355Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Despite recommendation by the British Association of Oncological Surgeons, adoption of clips outside the IMPORT trials has been slow [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. This is due, in part, to some persistent myths:‘Clips are unreliable because they migrate’No clip migration was seen in a recent study of 30 cases with paired clips placed at surgery [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. A serial computed tomography imaging study suggested that clips serve as a stable surrogate for the tumour bed over time [[16]Weed D.W. Yan D. Martinez A.A. Vicini F.A. Wilkinson T.J. Wong J. The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation.Int J Radiat Oncol Biol Phys. 2004; 60: 484-492Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. In this study of 28 patients, surgically placed clips in the lumpectomy cavity were imaged using X-ray computed tomography an average of 27 days apart. The clip and lumpectomy cavity moved a mean of 3 mm along the three principal Cartesian axes, providing strong radiographic surrogates for the biopsy cavity. If clips are inserted in pairs, migration can be easily detected if they part company.‘Clips increase the risk of postoperative infection’There is no evidence to support this: clips are routinely inserted in the axilla with no increased risk of infection.‘Clips take too long to put in’Clip insertion takes 1–2 min; surgeons participating in the current National Cancer Research Institute IMPORT trials confirm this.‘Clips are too expensive’Titanium clips cost around £1 (1€) for a pack of six, which can be inserted with a reusable ligaclip gun. Six pairs of clips are inserted in the surgical excision cavity wall, before any oncoplastic procedure, in the following locations: beneath the skin, at the deep fascia and at four radial locations (medial, lateral, superior and inferior).‘Surgeons will forget to insert the clips’There is possibly some truth in this, but mechanisms have been developed to facilitate the uptake of clip insertion. These include: using clip stickers to attach to the theatre list, liaising with the operation department practitioner and developing a league table for surgeons inserting clips. The most effective vehicle for the implementation of clip insertion has been adoption by the British Association of Oncological Surgeons [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar].Figure 2 shows an example of how useful clips can be for marking up the field borders of an electron boost on the patient's skin. As more and more radiotherapy centres use X-ray computed tomography to plan breast radiotherapy, this simple but accurate technique for localising the tumour bed represents a big step forward in improving standard treatment practices. This has already been introduced in 25 UK radiotherapy centres participating in the National Cancer Research Institute IMPORT LOW trial testing partial breast radiotherapy. For patients at these centres, the internal fiducials ensure that the gross tumour volume is accurately localised for all patients, not just those entered into the trial. In conclusion, the use of tumour bed clips for breast radiotherapy ticks all the boxes and is encouraged at all UK centres (see Table 1).Fig. 2The surgical excision scar is often an inaccurate marker of the tumour bed - here delineated by ligaclips.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 1Impact of titanium clips marking the tumour excision cavity wall in the breastProbably improve local controlNo increase in morbidity∗Morbidity will be reduced if the radiotherapy boost volume is smaller.National guidelines existLow costLittle/no impact on trainingUse of tumour bed clips√√√√√∗ Morbidity will be reduced if the radiotherapy boost volume is smaller. Open table in a new tab Accurate Boost Localisation is ImportantAfter complete microscopic resection of primary tumour in women with early breast cancer, most local tumour relapses present close to the primary tumour [[1]Mannino M. Yarnold J. Accelerated partial breast irradiation trials: diversity in rationale and design.Radiother Oncol. 2009; 91: 16-22Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. It is therefore important to ensure that the tumour bed lies well inside the treatment volume encompassed by tangential fields to the whole breast and subsequent tumour bed boost. The penalty for geographical miss is severe: four local tumour relapses cause, on average, one death from breast cancer [[2]Clarke M. Collins R. Darby S. et al.Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.Lancet. 2006; 366: 2087-2106Abstract Full Text Full Text PDF Scopus (3949) Google Scholar]. The optimal margin to add to the excision cavity for whole breast radiotherapy and the tumour bed boost remains controversial, but there is general agreement that the excision cavity itself must always lie inside the high dose envelope. After complete microscopic resection of primary tumour in women with early breast cancer, most local tumour relapses present close to the primary tumour [[1]Mannino M. Yarnold J. Accelerated partial breast irradiation trials: diversity in rationale and design.Radiother Oncol. 2009; 91: 16-22Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. It is therefore important to ensure that the tumour bed lies well inside the treatment volume encompassed by tangential fields to the whole breast and subsequent tumour bed boost. The penalty for geographical miss is severe: four local tumour relapses cause, on average, one death from breast cancer [[2]Clarke M. Collins R. Darby S. et al.Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.Lancet. 2006; 366: 2087-2106Abstract Full Text Full Text PDF Scopus (3949) Google Scholar]. The optimal margin to add to the excision cavity for whole breast radiotherapy and the tumour bed boost remains controversial, but there is general agreement that the excision cavity itself must always lie inside the high dose envelope. Boost Localisation is Currently Inaccurate and the Tumour Bed Sometimes Lies Outside Whole Breast TangentsThe tumour beds of medially and laterally located tumours are particularly prone to under-dosage if surface landmarks are used as fiducial points for whole breast radiotherapy planning (see Fig. 1) [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar]. It is therefore justified to restate the obvious: accurate tumour bed localisation is essential even for planning whole breast radiotherapy.It has been known for a very long time that clinical planning of the tumour bed boost volume based on preoperative imaging, surgical note and breast scar position is very unreliable [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar]. Increasingly, the breast scar is often placed some distance from the tumour for wire-guided localisation biopsy or better cosmetic outcome. In addition, the practice of oncoplastic surgery, whereby breast tissue is repositioned following wide local excision to minimise the surgical deficit, is becoming standard of care [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. In this situation, the preoperative imaging often bears very little relationship to the final position of the tumour bed.X-ray computed tomography or ultrasound imaging can use seroma as a surrogate for the tumour bed position, but there are limitations. First, the seroma is only clearly defined in around one-quarter of patients [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Second, the seroma underestimates the true extent of the tumour bed defined by implanted clips [[12]Coles C.E. Cash C.J. Treece G.M. et al.High definition three-dimensional ultrasound to localise the tumour bed: a breast radiotherapy planning study.Radiother Oncol. 2007; 84: 233-241Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]. In spectacular images collected by magnetic resonance, concentric rings of granulation tissue laid down in the wall of the excision cavity reduce the volume of seroma [[13]Whipp E.C. Halliwell M. Magnetic resonance imaging appearances in the postoperative breast: the clinical target volume-tumor and its relationship to the chest wall.Int J Radiat Oncol Biol Phys. 2008; 72: 49-57Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. This explains why the seroma is not a surrogate for the surgical cavity. The tumour beds of medially and laterally located tumours are particularly prone to under-dosage if surface landmarks are used as fiducial points for whole breast radiotherapy planning (see Fig. 1) [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar]. It is therefore justified to restate the obvious: accurate tumour bed localisation is essential even for planning whole breast radiotherapy. It has been known for a very long time that clinical planning of the tumour bed boost volume based on preoperative imaging, surgical note and breast scar position is very unreliable [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar]. Increasingly, the breast scar is often placed some distance from the tumour for wire-guided localisation biopsy or better cosmetic outcome. In addition, the practice of oncoplastic surgery, whereby breast tissue is repositioned following wide local excision to minimise the surgical deficit, is becoming standard of care [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. In this situation, the preoperative imaging often bears very little relationship to the final position of the tumour bed. X-ray computed tomography or ultrasound imaging can use seroma as a surrogate for the tumour bed position, but there are limitations. First, the seroma is only clearly defined in around one-quarter of patients [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Second, the seroma underestimates the true extent of the tumour bed defined by implanted clips [[12]Coles C.E. Cash C.J. Treece G.M. et al.High definition three-dimensional ultrasound to localise the tumour bed: a breast radiotherapy planning study.Radiother Oncol. 2007; 84: 233-241Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar]. In spectacular images collected by magnetic resonance, concentric rings of granulation tissue laid down in the wall of the excision cavity reduce the volume of seroma [[13]Whipp E.C. Halliwell M. Magnetic resonance imaging appearances in the postoperative breast: the clinical target volume-tumor and its relationship to the chest wall.Int J Radiat Oncol Biol Phys. 2008; 72: 49-57Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. This explains why the seroma is not a surrogate for the surgical cavity. Increasing the Margins is Not the AnswerUncertainty in localising the tumour bed in patients with medial or lateral tumours can be overcome by increasing the posterior field borders of whole breast tangents, but only at the expense of increased morbidity in the ribcage and lung, and potential mortality in women with left-sided tumours. The heart is the most sensitive organ, a few Gray being associated with increased risk of fatal heart disease, and every effort needs to be made to exclude the organ from the treatment volume [[14]Darby S.C. McGale P. Taylor C.W. Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries.Lancet Oncol. 2005; 6: 557-565Abstract Full Text Full Text PDF PubMed Scopus (787) Google Scholar]. When localising the tumour bed boost, increasing the clinical target volume is a crude way of avoiding geographical miss. This is particularly important in the emerging era of oncoplastic surgery, when the tumour bed may be well away from its primary location. Uncertainty in localising the tumour bed in patients with medial or lateral tumours can be overcome by increasing the posterior field borders of whole breast tangents, but only at the expense of increased morbidity in the ribcage and lung, and potential mortality in women with left-sided tumours. The heart is the most sensitive organ, a few Gray being associated with increased risk of fatal heart disease, and every effort needs to be made to exclude the organ from the treatment volume [[14]Darby S.C. McGale P. Taylor C.W. Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries.Lancet Oncol. 2005; 6: 557-565Abstract Full Text Full Text PDF PubMed Scopus (787) Google Scholar]. When localising the tumour bed boost, increasing the clinical target volume is a crude way of avoiding geographical miss. This is particularly important in the emerging era of oncoplastic surgery, when the tumour bed may be well away from its primary location. Clips are the Obvious SolutionAn audit of the use of tumour bed clips vs standard anatomical landmarks for whole breast radiotherapy showed that the addition of clips modified the field borders in 43% (13/30) of cases [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Numerous studies have shown the greater accuracy of titanium clips in tumour bed boost radiotherapy planning compared with clinical mark up [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar, 15Bates A.T. Swift C.L. Kwa W. Moravan V. Aquino-Parsons C. A computed tomography-based protocol vs conventional clinical mark-up for breast electron boost.Clin Oncol (R Coll Radiol). 2007; 19: 349-355Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Despite recommendation by the British Association of Oncological Surgeons, adoption of clips outside the IMPORT trials has been slow [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. This is due, in part, to some persistent myths:‘Clips are unreliable because they migrate’No clip migration was seen in a recent study of 30 cases with paired clips placed at surgery [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. A serial computed tomography imaging study suggested that clips serve as a stable surrogate for the tumour bed over time [[16]Weed D.W. Yan D. Martinez A.A. Vicini F.A. Wilkinson T.J. Wong J. The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation.Int J Radiat Oncol Biol Phys. 2004; 60: 484-492Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. In this study of 28 patients, surgically placed clips in the lumpectomy cavity were imaged using X-ray computed tomography an average of 27 days apart. The clip and lumpectomy cavity moved a mean of 3 mm along the three principal Cartesian axes, providing strong radiographic surrogates for the biopsy cavity. If clips are inserted in pairs, migration can be easily detected if they part company.‘Clips increase the risk of postoperative infection’There is no evidence to support this: clips are routinely inserted in the axilla with no increased risk of infection.‘Clips take too long to put in’Clip insertion takes 1–2 min; surgeons participating in the current National Cancer Research Institute IMPORT trials confirm this.‘Clips are too expensive’Titanium clips cost around £1 (1€) for a pack of six, which can be inserted with a reusable ligaclip gun. Six pairs of clips are inserted in the surgical excision cavity wall, before any oncoplastic procedure, in the following locations: beneath the skin, at the deep fascia and at four radial locations (medial, lateral, superior and inferior).‘Surgeons will forget to insert the clips’There is possibly some truth in this, but mechanisms have been developed to facilitate the uptake of clip insertion. These include: using clip stickers to attach to the theatre list, liaising with the operation department practitioner and developing a league table for surgeons inserting clips. The most effective vehicle for the implementation of clip insertion has been adoption by the British Association of Oncological Surgeons [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar].Figure 2 shows an example of how useful clips can be for marking up the field borders of an electron boost on the patient's skin. As more and more radiotherapy centres use X-ray computed tomography to plan breast radiotherapy, this simple but accurate technique for localising the tumour bed represents a big step forward in improving standard treatment practices. This has already been introduced in 25 UK radiotherapy centres participating in the National Cancer Research Institute IMPORT LOW trial testing partial breast radiotherapy. For patients at these centres, the internal fiducials ensure that the gross tumour volume is accurately localised for all patients, not just those entered into the trial. In conclusion, the use of tumour bed clips for breast radiotherapy ticks all the boxes and is encouraged at all UK centres (see Table 1).Table 1Impact of titanium clips marking the tumour excision cavity wall in the breastProbably improve local controlNo increase in morbidity∗Morbidity will be reduced if the radiotherapy boost volume is smaller.National guidelines existLow costLittle/no impact on trainingUse of tumour bed clips√√√√√∗ Morbidity will be reduced if the radiotherapy boost volume is smaller. Open table in a new tab An audit of the use of tumour bed clips vs standard anatomical landmarks for whole breast radiotherapy showed that the addition of clips modified the field borders in 43% (13/30) of cases [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. Numerous studies have shown the greater accuracy of titanium clips in tumour bed boost radiotherapy planning compared with clinical mark up [3Bedwinek J. Breast conserving surgery and irradiation: the importance of demarcating the excision cavity with surgical clips.Int J Radiat Oncol Biol Phys. 1993; 26: 675-679Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 4Krawczyk J.J. Engel B. The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation.Int J Radiat Oncol Biol Phys. 1999; 43: 347-350Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 5Denham J.W. Sillar R.W. Clarke D. Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss!.Clin Oncol (R Coll Radiol). 1991; 3: 257-261Abstract Full Text PDF PubMed Scopus (50) Google Scholar, 6Machtay M. Lanciano R. Hoffman J. Hanks G.E. Inaccuracies in using the lumpectomy scar for planning electron boosts in primary breast carcinoma.Int J Radiat Oncol Biol Phys. 1994; 30: 43-48Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 7Harrington K.J. Harrison M. Bayle P. et al.Surgical clips in planning the electron boost in breast cancer: a qualitative and quantitative evaluation.Int J Radiat Oncol Biol Phys. 1996; 34: 579-584Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 8Hunter M.A. McFall T.A. Hehr K.A. Breast-conserving surgery for primary breast cancer: necessity for surgical clips to define the tumor bed for radiation planning.Radiology. 1996; 200: 281-282PubMed Google Scholar, 9Kovner F. Agay R. Merimsky O. Stadler J. Klausner J. Inbar M. Clips and scar as the guidelines for breast radiation boost after lumpectomy.Eur J Surg Oncol. 1999; 25: 483-486Abstract Full Text PDF PubMed Scopus (47) Google Scholar, 15Bates A.T. Swift C.L. Kwa W. Moravan V. Aquino-Parsons C. A computed tomography-based protocol vs conventional clinical mark-up for breast electron boost.Clin Oncol (R Coll Radiol). 2007; 19: 349-355Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar]. Despite recommendation by the British Association of Oncological Surgeons, adoption of clips outside the IMPORT trials has been slow [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. This is due, in part, to some persistent myths:‘Clips are unreliable because they migrate’ No clip migration was seen in a recent study of 30 cases with paired clips placed at surgery [[11]Coles C.E. Wilson C.B. Cumming J. et al.Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.Eur J Surg Oncol. 2009; 35: 578-582Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. A serial computed tomography imaging study suggested that clips serve as a stable surrogate for the tumour bed over time [[16]Weed D.W. Yan D. Martinez A.A. Vicini F.A. Wilkinson T.J. Wong J. The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation.Int J Radiat Oncol Biol Phys. 2004; 60: 484-492Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar]. In this study of 28 patients, surgically placed clips in the lumpectomy cavity were imaged using X-ray computed tomography an average of 27 days apart. The clip and lumpectomy cavity moved a mean of 3 mm along the three principal Cartesian axes, providing strong radiographic surrogates for the biopsy cavity. If clips are inserted in pairs, migration can be easily detected if they part company.‘Clips increase the risk of postoperative infection’ There is no evidence to support this: clips are routinely inserted in the axilla with no increased risk of infection.‘Clips take too long to put in’ Clip insertion takes 1–2 min; surgeons participating in the current National Cancer Research Institute IMPORT trials confirm this.‘Clips are too expensive’ Titanium clips cost around £1 (1€) for a pack of six, which can be inserted with a reusable ligaclip gun. Six pairs of clips are inserted in the surgical excision cavity wall, before any oncoplastic procedure, in the following locations: beneath the skin, at the deep fascia and at four radial locations (medial, lateral, superior and inferior).‘Surgeons will forget to insert the clips’ There is possibly some truth in this, but mechanisms have been developed to facilitate the uptake of clip insertion. These include: using clip stickers to attach to the theatre list, liaising with the operation department practitioner and developing a league table for surgeons inserting clips. The most effective vehicle for the implementation of clip insertion has been adoption by the British Association of Oncological Surgeons [[10]Association of Breast Surgery at Baso 2009. Collaborators: Bishop H, Chan C, Monypenny I, Patnick J, Sibbering M, Watkins R, Winstanley J, Bundred N, Corder A, Nicholson S, Robertson J, Rothnie N, Davies L. Surgical guidelines for the management of breast cancer. Eur J Surg Oncol 2009; 35(Suppl. 1):1–22.Google Scholar]. Figure 2 shows an example of how useful clips can be for marking up the field borders of an electron boost on the patient's skin. As more and more radiotherapy centres use X-ray computed tomography to plan breast radiotherapy, this simple but accurate technique for localising the tumour bed represents a big step forward in improving standard treatment practices. This has already been introduced in 25 UK radiotherapy centres participating in the National Cancer Research Institute IMPORT LOW trial testing partial breast radiotherapy. For patients at these centres, the internal fiducials ensure that the gross tumour volume is accurately localised for all patients, not just those entered into the trial. In conclusion, the use of tumour bed clips for breast radiotherapy ticks all the boxes and is encouraged at all UK centres (see Table 1). C. Coles receives research funding from the Cambridge National Institute of Health Research Biomedical Research Centre.