Inr J Radmmn Oncology Bid Phys Vol. 20, pp. 177-178 Pnnted in the U S.A. All rights reserved.
0360.3016/91 $3.00 + .Xl Copyright 0 1991 Pergamon Press plc
??Editorial
TO BOOST
OR NOT TO BOOST,
ABRAM
RECHT,
M.D.
AND HOW TO DO IT
AND JAY R. HARRIS,
M.D.
Dept. of Radiation Therapy, Harvard Medical School, and Joint Center for Radiation Therapy, Boston, MA Breast cancer, Radiotherapy,
Boost, Treatment planning.
The function of a “boost” dose in radiotherapy
is to give a higher dose to an area thought to have a higher tumor burden than the surrounding tissue. By restricting the high-dose region to a part of the target volume rather than the entire volume, the use of a boost might reduce the incidence of local failure, while avoiding complications that would result from treating the entire volume to the full dose given to the boost volume. One setting where a boost is commonly, but not universally, performed is in breast cancer patients treated with definitive radiotherapy. In practice, the use of a boost in this setting could result in a higher complication rate or a worsened cosmetic outcome than if a boost were not used. Further, the use of a boost adds to the complexity, duration, and expense of treatment, particularly when interstitial implantation is used, and an advantage in local tumor control has not been demonstrated. For these reasons, the use of a boost is still controversial. The main rationale for using a boost is the observed distribution of tumor in the breast. In a study of mastectomy specimens (4), the location and type of tumor foci found beyond the edge of the reference tumor mass were carefully mapped using a radiologic-pathologic correlation technique. In many breasts, tumor foci were discovered well beyond the boundaries of a cosmetically-acceptable surgical resection. However, most of the residual tumor was relatively close to the reference tumor mass. This finding likely explains why the majority of breast failures following treatment with conservative surgery and radiotherapy are at or near the site of the primary tumor (1, 6). This also suggests that the use of a boost will improve the likelihood of local control. The major evidence against the need to use a boost as a standard part of treatment is the results of the NSABP B-06 trial, in which no boost was used. This study resulted
Reprint requests to: Abram Recht, M.D., Joint Center Radiation
Therapy.
50 Binney St., Boston.
in an 8-year risk of a breast relapse after lumpectomy and radiotherapy of lo%, comparable to that found at other institutions when a boost was used (3). However, the absence of the routine and uniform use of tissue compensators as part of the radiotherapy technique of the NSABP trial may have resulted in an increased inhomogeneity of the dosage of radiation and a greater effective dose to the tumor site than the nominal dose of 50 to 53 Gy. Note also that these patients had “negative” histologic resection margins; although this may have improved the overall results, such a selection factor may also result in some patients undergoing mastectomy who could actually have been satisfactorally treated with conservative surgery and radiotherapy. Assuming that the use of a boost is desirable, there appears to be little difference in outcome between patients treated with interstitial implantation or electron beams (7, 10). Hence, the expense, hospitalization, and discomfort associated with implantation can be avoided. Even with implantation, however, the impact of a boost of moderate size and dose on the cosmetic results of treatment is small (5), so that either approach is reasonable. If a boost is to be used, then it is important that it be done correctly; that is, the proper target volume should be adequately localized and treated. The boost is not intended to treat the scar itself but rather the bed of excision and immediately surrounding tissue. In most situations, the scar would be an adequate guide to the location of the tumor ifthe surgeon placed the incision directly over the tumor. However, such is not always the case. The location of the surgical scar is especially problematic with mammographically-guided excisions. Although the preoperative description of the lesion, mammograms, operative note, and physical findings of surgical induration can be very helpful in defining the tumor location in the absence
for
Accepted
MA 021 15.
177
for publication
27 July 1990.
178
I. J. Radiation Oncology 0 Biology 0 Physics
of a surgical scar that accurately represents its position, these tools are subject to considerable uncertainty and variability. In this setting, the article by Regine et al. (8) in this issue of the Journal provides an elegant and accurate solution to the problem of localizing the tumor bed. The authors describe how CT scanning can be used to identify the region of the boost volume precisely. This approach requires that the surgeon place clips in the excision bed, and this is not uniformly done throughout the country. If clips are placed, however, they could in principle be used to locate the target volume by use of the simulator alone, if CT planning is not available (i.e., by aligning the scar and clips in a “beam’s-eye” view). There are also ways of using the simulator to determine the depth of the tumor bed, without a CT scan (9). Topics for future investigation include the question of which patients will benefit from a boost. The utility of a boost must be considered in relation to the extent of surgical resection. It is likely that a boost is more important after routine excisional biopsy than after very wide excision or quadrantectomy. A related controversy exists as to whether patients with microscopically uninvolved margins benefit from a boost. A cooperative randomized study of this issue (for patients with negative histologic resection margins) is to be started in 1990 by the European Organization for Research and Treatment of Cancer. Whether a difference will be appreciable even with a large multi-institutional trial is uncertain. Although there are no definitive data on the subject, we believe that the absolute difference in local control is unlikely to be greater than 5% (for all patients grouped together), given current
January 1991, Volume 20, Number 1
practice regarding patient selection and surgery. Although this is a clinically significant difference, the number of patients required to prove this statistically is in the thousands. Among other questions open to speculation currently are what volume should be included within the boost field and what dose should be given. These might perhaps be best determined eventually by taking into account the extent of surgical resection and the histology of the tumor, and possibly other factors as well. Usually we use 2 to 3 cm margins around the tumor bed, giving a dose of 16 Gy in 8 fractions, prescribed to the 80% isodose line, using electrons of sufficient energy to bring this line to near or at the anterior chest wall. There is also a question regarding the optimal orientation of the boost. We believe that it may be better to orient the boost so as to cover the area of potential spread along the ducts radially (i.e., toward and away from the nipple), particularly in patients with a prominant component of ductal carcinoma in situ. (Anatomic studies directed at confirming this are in process.) At present, given the difficulty of interpreting the meaning of a “negative” resection margin (2) and the ease of administration and low extra morbidity of giving an electron or photon boost, we believe that a boost should be routinely used for all patients, except perhaps those who have had very wide surgical resections with negative margins. The study by Regine et al. (8) properly emphasizes the need for the radiotherapist to identify accurately the target volume to be boosted. If clips are placed at the time of excision, CT scanning is one method available to accomplish this.
REFERENCES 1.
2.
3.
4.
5.
Boyages, J.; Recht, A.; Connolly, J.; Schnitt, S.; Kooy, H.; Love, S.; Osteen, R. T.; Cady, B.; Silver, B.; Harris, J. R. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother. Oncol. 19:29-4 1; 1990. Connolly, J. L.; Schnitt, S. J. Evaluation of biopsy specimens in patients considered for treatment by conservative surgery and radiation therapy for breast cancer. Pathol. Ann. 23(Pt l):l-23; 1988. Fisher, B.; Redmond, C.; Poisson, R.; Margolese, R.; Wolmark, N.; Wickerham, L.; Fisher, E.; Deutsch, M.; Caplan, R.; Pilch, Y.; Glass, A.; Shibata, H.; Lemer, H.; Terz, J.; Sidorovich, L. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N. Engl. J. Med. 320:822-828; 1989. Holland, R.; Connolly, J. L.; Gelman, R.; Mravunac, M.; Hendriks, J. H. C. L.; Verbeek, A. L. M.; Schnitt, S. J.; Silver, B.; Boyages, J.; Harris, J. R. The presence of an extensive intraductal component (EIC) following a limited excision predicts for prominent residual disease in the remainder of the breast. J. Clin. Oncol. 8: 113- 118; 1990. Olivotto, 1. A.; Rose, M. A.; Osteen, R. T.; Love, S.; Cady, B.; Silver, B.; Recht, A.; Harris, J. R. Late cosmetic outcome
6.
7.
8.
9.
10.
after conservative surgery and radiotherapy for early breast cancer: analysis of causes of cosmetic failure. Int. J. Radiat. Oncol. Biol. Phys. 17:747-753; 1989. Recht, A.: Silen, W.; Schnitt, S. J.: Connolly, J. L.; Gelman, R. S.; Rose, M. A.; Silver, B.: Harris, J. R. Time-course of local recurrence following conservative surgery and radiotherapy for breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 15:255-261; 1988. Recht, A.; Triedman, S. A.; Harris, J. R. The “boost” in the treatment of early stage breast cancer: electrons vs. interstital implants. Front. Radiat. Ther. Oncol. (In press). Regine, R. F.; Ayyangar, K. M.; Komarnicky, L. T.; Bhandare, N.; Mansfield, C. M. Computer-CT planning of the electron boost in definitive breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 20:121-125; 1991. Solin, L. J.; Chu, J. C. H.; Larsen, R.; Fowble, B.: Galvin, J. M.; Goodman, R. L. Determination of depth for electron breast boosts. Int. J. Radiat. Oncol. Biol. Phys. 13: 19151919; 1987. Triedman, S.; Boyages, J.; Silver, B.; Recht, A.; Harris, J. A comparison of local control and cosmetic outcome in patients boosted with electrons (E) or implant (I) in the conservative management of early breast carcinoma (Abstr.). Proc. 17th Intl. Congress Radio]., Paris, July 1989.
0360.3016/91 $3.00 + .Xl Copyright 0 1991 Pergamon Press plc
??Editorial
TO BOOST
OR NOT TO BOOST,
ABRAM
RECHT,
M.D.
AND HOW TO DO IT
AND JAY R. HARRIS,
M.D.
Dept. of Radiation Therapy, Harvard Medical School, and Joint Center for Radiation Therapy, Boston, MA Breast cancer, Radiotherapy,
Boost, Treatment planning.
The function of a “boost” dose in radiotherapy
is to give a higher dose to an area thought to have a higher tumor burden than the surrounding tissue. By restricting the high-dose region to a part of the target volume rather than the entire volume, the use of a boost might reduce the incidence of local failure, while avoiding complications that would result from treating the entire volume to the full dose given to the boost volume. One setting where a boost is commonly, but not universally, performed is in breast cancer patients treated with definitive radiotherapy. In practice, the use of a boost in this setting could result in a higher complication rate or a worsened cosmetic outcome than if a boost were not used. Further, the use of a boost adds to the complexity, duration, and expense of treatment, particularly when interstitial implantation is used, and an advantage in local tumor control has not been demonstrated. For these reasons, the use of a boost is still controversial. The main rationale for using a boost is the observed distribution of tumor in the breast. In a study of mastectomy specimens (4), the location and type of tumor foci found beyond the edge of the reference tumor mass were carefully mapped using a radiologic-pathologic correlation technique. In many breasts, tumor foci were discovered well beyond the boundaries of a cosmetically-acceptable surgical resection. However, most of the residual tumor was relatively close to the reference tumor mass. This finding likely explains why the majority of breast failures following treatment with conservative surgery and radiotherapy are at or near the site of the primary tumor (1, 6). This also suggests that the use of a boost will improve the likelihood of local control. The major evidence against the need to use a boost as a standard part of treatment is the results of the NSABP B-06 trial, in which no boost was used. This study resulted
Reprint requests to: Abram Recht, M.D., Joint Center Radiation
Therapy.
50 Binney St., Boston.
in an 8-year risk of a breast relapse after lumpectomy and radiotherapy of lo%, comparable to that found at other institutions when a boost was used (3). However, the absence of the routine and uniform use of tissue compensators as part of the radiotherapy technique of the NSABP trial may have resulted in an increased inhomogeneity of the dosage of radiation and a greater effective dose to the tumor site than the nominal dose of 50 to 53 Gy. Note also that these patients had “negative” histologic resection margins; although this may have improved the overall results, such a selection factor may also result in some patients undergoing mastectomy who could actually have been satisfactorally treated with conservative surgery and radiotherapy. Assuming that the use of a boost is desirable, there appears to be little difference in outcome between patients treated with interstitial implantation or electron beams (7, 10). Hence, the expense, hospitalization, and discomfort associated with implantation can be avoided. Even with implantation, however, the impact of a boost of moderate size and dose on the cosmetic results of treatment is small (5), so that either approach is reasonable. If a boost is to be used, then it is important that it be done correctly; that is, the proper target volume should be adequately localized and treated. The boost is not intended to treat the scar itself but rather the bed of excision and immediately surrounding tissue. In most situations, the scar would be an adequate guide to the location of the tumor ifthe surgeon placed the incision directly over the tumor. However, such is not always the case. The location of the surgical scar is especially problematic with mammographically-guided excisions. Although the preoperative description of the lesion, mammograms, operative note, and physical findings of surgical induration can be very helpful in defining the tumor location in the absence
for
Accepted
MA 021 15.
177
for publication
27 July 1990.
178
I. J. Radiation Oncology 0 Biology 0 Physics
of a surgical scar that accurately represents its position, these tools are subject to considerable uncertainty and variability. In this setting, the article by Regine et al. (8) in this issue of the Journal provides an elegant and accurate solution to the problem of localizing the tumor bed. The authors describe how CT scanning can be used to identify the region of the boost volume precisely. This approach requires that the surgeon place clips in the excision bed, and this is not uniformly done throughout the country. If clips are placed, however, they could in principle be used to locate the target volume by use of the simulator alone, if CT planning is not available (i.e., by aligning the scar and clips in a “beam’s-eye” view). There are also ways of using the simulator to determine the depth of the tumor bed, without a CT scan (9). Topics for future investigation include the question of which patients will benefit from a boost. The utility of a boost must be considered in relation to the extent of surgical resection. It is likely that a boost is more important after routine excisional biopsy than after very wide excision or quadrantectomy. A related controversy exists as to whether patients with microscopically uninvolved margins benefit from a boost. A cooperative randomized study of this issue (for patients with negative histologic resection margins) is to be started in 1990 by the European Organization for Research and Treatment of Cancer. Whether a difference will be appreciable even with a large multi-institutional trial is uncertain. Although there are no definitive data on the subject, we believe that the absolute difference in local control is unlikely to be greater than 5% (for all patients grouped together), given current
January 1991, Volume 20, Number 1
practice regarding patient selection and surgery. Although this is a clinically significant difference, the number of patients required to prove this statistically is in the thousands. Among other questions open to speculation currently are what volume should be included within the boost field and what dose should be given. These might perhaps be best determined eventually by taking into account the extent of surgical resection and the histology of the tumor, and possibly other factors as well. Usually we use 2 to 3 cm margins around the tumor bed, giving a dose of 16 Gy in 8 fractions, prescribed to the 80% isodose line, using electrons of sufficient energy to bring this line to near or at the anterior chest wall. There is also a question regarding the optimal orientation of the boost. We believe that it may be better to orient the boost so as to cover the area of potential spread along the ducts radially (i.e., toward and away from the nipple), particularly in patients with a prominant component of ductal carcinoma in situ. (Anatomic studies directed at confirming this are in process.) At present, given the difficulty of interpreting the meaning of a “negative” resection margin (2) and the ease of administration and low extra morbidity of giving an electron or photon boost, we believe that a boost should be routinely used for all patients, except perhaps those who have had very wide surgical resections with negative margins. The study by Regine et al. (8) properly emphasizes the need for the radiotherapist to identify accurately the target volume to be boosted. If clips are placed at the time of excision, CT scanning is one method available to accomplish this.
REFERENCES 1.
2.
3.
4.
5.
Boyages, J.; Recht, A.; Connolly, J.; Schnitt, S.; Kooy, H.; Love, S.; Osteen, R. T.; Cady, B.; Silver, B.; Harris, J. R. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother. Oncol. 19:29-4 1; 1990. Connolly, J. L.; Schnitt, S. J. Evaluation of biopsy specimens in patients considered for treatment by conservative surgery and radiation therapy for breast cancer. Pathol. Ann. 23(Pt l):l-23; 1988. Fisher, B.; Redmond, C.; Poisson, R.; Margolese, R.; Wolmark, N.; Wickerham, L.; Fisher, E.; Deutsch, M.; Caplan, R.; Pilch, Y.; Glass, A.; Shibata, H.; Lemer, H.; Terz, J.; Sidorovich, L. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N. Engl. J. Med. 320:822-828; 1989. Holland, R.; Connolly, J. L.; Gelman, R.; Mravunac, M.; Hendriks, J. H. C. L.; Verbeek, A. L. M.; Schnitt, S. J.; Silver, B.; Boyages, J.; Harris, J. R. The presence of an extensive intraductal component (EIC) following a limited excision predicts for prominent residual disease in the remainder of the breast. J. Clin. Oncol. 8: 113- 118; 1990. Olivotto, 1. A.; Rose, M. A.; Osteen, R. T.; Love, S.; Cady, B.; Silver, B.; Recht, A.; Harris, J. R. Late cosmetic outcome
6.
7.
8.
9.
10.
after conservative surgery and radiotherapy for early breast cancer: analysis of causes of cosmetic failure. Int. J. Radiat. Oncol. Biol. Phys. 17:747-753; 1989. Recht, A.: Silen, W.; Schnitt, S. J.: Connolly, J. L.; Gelman, R. S.; Rose, M. A.; Silver, B.: Harris, J. R. Time-course of local recurrence following conservative surgery and radiotherapy for breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 15:255-261; 1988. Recht, A.; Triedman, S. A.; Harris, J. R. The “boost” in the treatment of early stage breast cancer: electrons vs. interstital implants. Front. Radiat. Ther. Oncol. (In press). Regine, R. F.; Ayyangar, K. M.; Komarnicky, L. T.; Bhandare, N.; Mansfield, C. M. Computer-CT planning of the electron boost in definitive breast irradiation. Int. J. Radiat. Oncol. Biol. Phys. 20:121-125; 1991. Solin, L. J.; Chu, J. C. H.; Larsen, R.; Fowble, B.: Galvin, J. M.; Goodman, R. L. Determination of depth for electron breast boosts. Int. J. Radiat. Oncol. Biol. Phys. 13: 19151919; 1987. Triedman, S.; Boyages, J.; Silver, B.; Recht, A.; Harris, J. A comparison of local control and cosmetic outcome in patients boosted with electrons (E) or implant (I) in the conservative management of early breast carcinoma (Abstr.). Proc. 17th Intl. Congress Radio]., Paris, July 1989.
