- Email: [email protected]
S21 Intraoperative Radiation Therapy to the Breast
$8
Session 5. Innovations in Local Treatments: Surgery and Radiotherapy
to identify foci of cancer not seen on mammography. We studied the use of whole breast US in 426 Stage I and II patients. Although 75 (18%) had additional US detected abnormalities, only 12 (2.8%) were malignant. Eight of these 12 patients required mastectomy. Patient and tumor characteristics did not distinguish between patients with benign and malignant US findings. Studies of MRI in women with known breast cancer report the identification of additional foci of malignancy in 11% to 34% of women. The most common change in surgical therapy as a result of MRI findings is mastectomy. While this might seem to be appropriate, it is important to recognize that detailed pathology studies have documented additional tumor foci in 30-60% of patients with apparently localized breast cancer. In the 1970's, these studies served as the basis for the argument that mastectomy was the necessary treatment for all breast cancer. Extensive clinical experience has proven that the majority of these tumor foci are controlled with radiation, yet the ability to identify these loci with MRI or US is considered an indication for mastectomy. Evidence of clinical benefit in terms of overall survival, disease free survival, or quality of life is an established standard for the adoption of new therapeutic modalities in breast cancer. When imaging studies are used to select therapy, the same rigorous standards must be employed. To date, no evidence of benefit to the patient in the form of a reduced risk of ipsilateral breast tumor recurrence has been demonstrated in any MRI study. Until such data is available, the use of MRI to select surgical treatments is inappropriate outside of a clinical trial.
Nipple Sparing Mastectomy in Association with Intra [$20• Operative Radiotherapy: A New Type of Mastectomy for Breast Cancer Treatment J.P. Petit. European Institute of Oncology, Milano, Italy
Background. Breast conserving surgery has become the standard approach for about 80% of patients treated for primary breast cancer in most Centres. However, a mastectomy is still required in case of multicentric and/or large tumours or recurrences after conservative treatment. Although the removal of the nipple areola complex (NAC) increases the feeling of mutilation, the risk of local recurrences under the areola remains a strong argument in favour of the NAC removal when a mastectomy is required. It has been proven that adjuvant radiotherapy decreases the risk of local recurrence after conservative treatment as well as after mastectomy. Taking in account our recent experience of intra operative radiotherapy at the EIO (ELIOT) as well as the results of other teams using also protocols of intra operative radiotherapy, we published a pilot study demonstrating the feasibility of the technique in a series of 25 patients. More than 300 NSM have been performed I our institute since March 2002. Results: Among the 301 cases, 35 have been cancelled due to carcinoma found behind the areola at the frozen section. Invasive carcinoma was found in 58% of the cases and in situ carcinoma in 42%. The indications were large or multicentric tumours and/or diffuse microcalcifications distant from the NAC. On definitive histological examination, 25 patients were found to have positive margins under the areola (23 in situ and 4 infiltrating carcinoma). Twentyfour patients developed a superficial skin areolar slough followed by spontaneous healing and 9 patients lost their NAC due to total necrosis. Among these, one patient had a poor cosmetic result on the areola with asymmetrical location and required further surgical removal and reconstruction with tattoo and local flap in a better position. When rating the results from 0 (bad) to 10 (excellent), in average, the colour of the areola was rated 8/10, the sensitivity of nipple 2/10, the global esthetic result was rated 7/10 by the surgeon and 8 by the patients. According to the same scale, the rating of the radiodystrophy (pigmentation) was 9. No radionecrosis has been observed in this series. The short follow-up does not allow for any definitive conclusions concerning the recurrence rate. However, two recurrences have been observed. Both were observed far from the preserved areola. Preliminary results of the psychological study show a very high satisfaction with the preservation of the nipple (97.6%), with younger women expressing a higher satisfaction than older counterparts
~-~
Intraoperative Radiation Therapy to the Breast
R. Orecchia. European Institute of Oncology, Milano, Italy The term Intraoperative Radiotherapy (IORT) refers to the application of radiation during a surgical intervention, after the removal of a neoplastic mass. The rationale for the use of this segmental RT in place of whole-breast irradiation is based on the results of some studies reporting that local relapses, after conservative surgery and RT, occur at the original tumour site at a rate of 80% or more. With IOERT is possible to reduce the radiation field only to the involved quadrant of the breast and change the RT course from 57 weeks to one single dose in the operating theatre immediately following surgical resection. An innovative aspect of the IOERT is represented by the
Thursday, 27 January 2005
possibility of overcoming some constraints such as the accessibility to the centres of RT, the socio-economic impact on the working life and on the personal habits of the patient. Moreover IOERT could minimise some clinical problems related to the side effects since the skin and the subcutaneous tissue are not irradiated and the spread of irradiation to lung and heart is reduced. Another advantage is the avoidance of the interactions with the systemic therapy, that may determine delays in the initiation or in the carrying out of the conventional treatment. At the lEO our intraoperative technique has been named ELIOT (Electron Intra Operative Therapy). After the first patients were successfully treated on July 1999, the clinical experience was planned and developed in 4 phases: - A dose-escalation study in order to define the maximum tolerate dose in single fraction. This phase was closed in April 2000 with 58 patients treated. - A phase II study(from May to November 2000) at the maximum tolerated dose level reached (21 Gy.) - A prospective randomised phase III study (started in December 2000)comparing standard EBRT with a single dose (21 Gy) of ELIOT. Up to November 2004, about 700 randomised patients have been included on this study - A nipple-sparing mastectomy study (since March 2002) testing a new technique to preserve the nipple-areola complex (NAC) during mastectomy, which includes the delivery of a 16 Gy single dose (220 patients up to November 2004). The total number of patients involved in all of the above-mentioned studies is more than 700. Another 250 patients outside the randomised study had been treated with ELIOT at 21 Gy after breast conserving surgery at their own request. The results of these studies will be presented and discussed.
[
S
•
Which extent of Adjuvant Radiotherapy is Standard?
J. Bellon, J. Harris. Dana-Farber Cancer Institute, United States of America Radiotherapy (RT) is used in patients with invasive breast cancer treated with mastectomy or with breast-conserving surgery. This review will summarize the latest information (primarily from randomized clinical trials) regarding the indications for RT and, if indicated, what volumes should be irradiated. There are a couple of major themes regarding the use of adjuvant RT. One is the important issue of assessing its value separately when used in the absence or when used in conjunction with adjuvant systemic therapy. Adjuvant systemic therapy (hormonal therapy and/or chemotherapy) is now typically used in patients with invasive breast cancer. In the absence of systemic therapy, RT reduces local recurrence after either mastectomy or breast conserving surgery by about 70%. Theoretically, the use of adjuvant systemic therapy by itself might lower local recurrence lessening the need for RT, interact with RT to make RT more or less effective and/or provide 'spatial' complementation (RT for local and systemic therapy for systemic disease) to improve survival when both are used. What has, in fact, been seen is that serendipitously systemic therapies (hormonal therapy more than chemotherapy) interact with RT to substantially improve local tumor control. More importantly, is the finding that when used with systemic therapy, RT decreases distant metastases and improves survival. Earlier studies, such as NSABP Trial B-04, where systemic therapy was not used, found that RT did not influence survival. This new information suggests that when systemic therapy is effective at controlling micro-metastatic disease, it is important to obtain local tumor control. Eventually, it is anticipated that systemic therapy will advance in its effectiveness so that no local therapy is needed; however, up to now, the use of systemic therapy has increased the role of local therapy. Another major theme is the need to balance the benefits of RT against its costs, complications and inconvenience. One of the most serious complications seen with RT for breast cancer, particularly for left-sided cancers, is increased late cardiac mortality. Early techniques of breast cancer RT, especially those techniques which intended to treat the internal mammary nodes, resulted in substantial doses of RT to the heart. It is fortunate that improved RT techniques, especially with the use of CT-based simulation, typically allow for exclusion of the entire heart in the high-dose areas. Efforts are continuing to identify patients who don't require RT. At present, there are no 'predictive' factors for RT; i.e., the benefit from RT in reducing local recurrence is proportionally similar in all subgroups. Therefore, the emphasis has been on identifying 'prognostic' factors where the risk of local recurrence without RT is sufficiently low such that RT is not justified. One of the latest innovations is that by restricting RT to only the part of the breast that contained the primary cancer, the daily dose of RT can be increased and treatment can be completed in one week rather than five to six weeks. It is also hoped that in addition to making RT more convenient, such accelerated partial breast irradiation (APBI) might lessen complications and increase the utilization of breast-conserving therapy. Once it is determined that adjuvant RT is indicated, the secondary question is "what volumes should be irradiated?" After mastectomy, the chest wall is always irradiated. After breast-conserving surgery, the conventional treatment is whole breast irradiation with APBI emerging as an attractive, but unproven, alternative. In both settings, the optimal extent of nodal irradiation (axillary, supraclavicular, and/or internal mammary) remains uncertain. Until
Session 5. Innovations in Local Treatments: Surgery and Radiotherapy
to identify foci of cancer not seen on mammography. We studied the use of whole breast US in 426 Stage I and II patients. Although 75 (18%) had additional US detected abnormalities, only 12 (2.8%) were malignant. Eight of these 12 patients required mastectomy. Patient and tumor characteristics did not distinguish between patients with benign and malignant US findings. Studies of MRI in women with known breast cancer report the identification of additional foci of malignancy in 11% to 34% of women. The most common change in surgical therapy as a result of MRI findings is mastectomy. While this might seem to be appropriate, it is important to recognize that detailed pathology studies have documented additional tumor foci in 30-60% of patients with apparently localized breast cancer. In the 1970's, these studies served as the basis for the argument that mastectomy was the necessary treatment for all breast cancer. Extensive clinical experience has proven that the majority of these tumor foci are controlled with radiation, yet the ability to identify these loci with MRI or US is considered an indication for mastectomy. Evidence of clinical benefit in terms of overall survival, disease free survival, or quality of life is an established standard for the adoption of new therapeutic modalities in breast cancer. When imaging studies are used to select therapy, the same rigorous standards must be employed. To date, no evidence of benefit to the patient in the form of a reduced risk of ipsilateral breast tumor recurrence has been demonstrated in any MRI study. Until such data is available, the use of MRI to select surgical treatments is inappropriate outside of a clinical trial.
Nipple Sparing Mastectomy in Association with Intra [$20• Operative Radiotherapy: A New Type of Mastectomy for Breast Cancer Treatment J.P. Petit. European Institute of Oncology, Milano, Italy
Background. Breast conserving surgery has become the standard approach for about 80% of patients treated for primary breast cancer in most Centres. However, a mastectomy is still required in case of multicentric and/or large tumours or recurrences after conservative treatment. Although the removal of the nipple areola complex (NAC) increases the feeling of mutilation, the risk of local recurrences under the areola remains a strong argument in favour of the NAC removal when a mastectomy is required. It has been proven that adjuvant radiotherapy decreases the risk of local recurrence after conservative treatment as well as after mastectomy. Taking in account our recent experience of intra operative radiotherapy at the EIO (ELIOT) as well as the results of other teams using also protocols of intra operative radiotherapy, we published a pilot study demonstrating the feasibility of the technique in a series of 25 patients. More than 300 NSM have been performed I our institute since March 2002. Results: Among the 301 cases, 35 have been cancelled due to carcinoma found behind the areola at the frozen section. Invasive carcinoma was found in 58% of the cases and in situ carcinoma in 42%. The indications were large or multicentric tumours and/or diffuse microcalcifications distant from the NAC. On definitive histological examination, 25 patients were found to have positive margins under the areola (23 in situ and 4 infiltrating carcinoma). Twentyfour patients developed a superficial skin areolar slough followed by spontaneous healing and 9 patients lost their NAC due to total necrosis. Among these, one patient had a poor cosmetic result on the areola with asymmetrical location and required further surgical removal and reconstruction with tattoo and local flap in a better position. When rating the results from 0 (bad) to 10 (excellent), in average, the colour of the areola was rated 8/10, the sensitivity of nipple 2/10, the global esthetic result was rated 7/10 by the surgeon and 8 by the patients. According to the same scale, the rating of the radiodystrophy (pigmentation) was 9. No radionecrosis has been observed in this series. The short follow-up does not allow for any definitive conclusions concerning the recurrence rate. However, two recurrences have been observed. Both were observed far from the preserved areola. Preliminary results of the psychological study show a very high satisfaction with the preservation of the nipple (97.6%), with younger women expressing a higher satisfaction than older counterparts
~-~
Intraoperative Radiation Therapy to the Breast
R. Orecchia. European Institute of Oncology, Milano, Italy The term Intraoperative Radiotherapy (IORT) refers to the application of radiation during a surgical intervention, after the removal of a neoplastic mass. The rationale for the use of this segmental RT in place of whole-breast irradiation is based on the results of some studies reporting that local relapses, after conservative surgery and RT, occur at the original tumour site at a rate of 80% or more. With IOERT is possible to reduce the radiation field only to the involved quadrant of the breast and change the RT course from 57 weeks to one single dose in the operating theatre immediately following surgical resection. An innovative aspect of the IOERT is represented by the
Thursday, 27 January 2005
possibility of overcoming some constraints such as the accessibility to the centres of RT, the socio-economic impact on the working life and on the personal habits of the patient. Moreover IOERT could minimise some clinical problems related to the side effects since the skin and the subcutaneous tissue are not irradiated and the spread of irradiation to lung and heart is reduced. Another advantage is the avoidance of the interactions with the systemic therapy, that may determine delays in the initiation or in the carrying out of the conventional treatment. At the lEO our intraoperative technique has been named ELIOT (Electron Intra Operative Therapy). After the first patients were successfully treated on July 1999, the clinical experience was planned and developed in 4 phases: - A dose-escalation study in order to define the maximum tolerate dose in single fraction. This phase was closed in April 2000 with 58 patients treated. - A phase II study(from May to November 2000) at the maximum tolerated dose level reached (21 Gy.) - A prospective randomised phase III study (started in December 2000)comparing standard EBRT with a single dose (21 Gy) of ELIOT. Up to November 2004, about 700 randomised patients have been included on this study - A nipple-sparing mastectomy study (since March 2002) testing a new technique to preserve the nipple-areola complex (NAC) during mastectomy, which includes the delivery of a 16 Gy single dose (220 patients up to November 2004). The total number of patients involved in all of the above-mentioned studies is more than 700. Another 250 patients outside the randomised study had been treated with ELIOT at 21 Gy after breast conserving surgery at their own request. The results of these studies will be presented and discussed.
[
S
•
Which extent of Adjuvant Radiotherapy is Standard?
J. Bellon, J. Harris. Dana-Farber Cancer Institute, United States of America Radiotherapy (RT) is used in patients with invasive breast cancer treated with mastectomy or with breast-conserving surgery. This review will summarize the latest information (primarily from randomized clinical trials) regarding the indications for RT and, if indicated, what volumes should be irradiated. There are a couple of major themes regarding the use of adjuvant RT. One is the important issue of assessing its value separately when used in the absence or when used in conjunction with adjuvant systemic therapy. Adjuvant systemic therapy (hormonal therapy and/or chemotherapy) is now typically used in patients with invasive breast cancer. In the absence of systemic therapy, RT reduces local recurrence after either mastectomy or breast conserving surgery by about 70%. Theoretically, the use of adjuvant systemic therapy by itself might lower local recurrence lessening the need for RT, interact with RT to make RT more or less effective and/or provide 'spatial' complementation (RT for local and systemic therapy for systemic disease) to improve survival when both are used. What has, in fact, been seen is that serendipitously systemic therapies (hormonal therapy more than chemotherapy) interact with RT to substantially improve local tumor control. More importantly, is the finding that when used with systemic therapy, RT decreases distant metastases and improves survival. Earlier studies, such as NSABP Trial B-04, where systemic therapy was not used, found that RT did not influence survival. This new information suggests that when systemic therapy is effective at controlling micro-metastatic disease, it is important to obtain local tumor control. Eventually, it is anticipated that systemic therapy will advance in its effectiveness so that no local therapy is needed; however, up to now, the use of systemic therapy has increased the role of local therapy. Another major theme is the need to balance the benefits of RT against its costs, complications and inconvenience. One of the most serious complications seen with RT for breast cancer, particularly for left-sided cancers, is increased late cardiac mortality. Early techniques of breast cancer RT, especially those techniques which intended to treat the internal mammary nodes, resulted in substantial doses of RT to the heart. It is fortunate that improved RT techniques, especially with the use of CT-based simulation, typically allow for exclusion of the entire heart in the high-dose areas. Efforts are continuing to identify patients who don't require RT. At present, there are no 'predictive' factors for RT; i.e., the benefit from RT in reducing local recurrence is proportionally similar in all subgroups. Therefore, the emphasis has been on identifying 'prognostic' factors where the risk of local recurrence without RT is sufficiently low such that RT is not justified. One of the latest innovations is that by restricting RT to only the part of the breast that contained the primary cancer, the daily dose of RT can be increased and treatment can be completed in one week rather than five to six weeks. It is also hoped that in addition to making RT more convenient, such accelerated partial breast irradiation (APBI) might lessen complications and increase the utilization of breast-conserving therapy. Once it is determined that adjuvant RT is indicated, the secondary question is "what volumes should be irradiated?" After mastectomy, the chest wall is always irradiated. After breast-conserving surgery, the conventional treatment is whole breast irradiation with APBI emerging as an attractive, but unproven, alternative. In both settings, the optimal extent of nodal irradiation (axillary, supraclavicular, and/or internal mammary) remains uncertain. Until