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8 Invited Localised treatment in breast cancer: intraoperative radiation therapy (IORT)
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Wednesday, 18 September 2002
Symposia HOW TO MANAGE EARLY BREAST CANCER ? 7
Invited
The impact o f a boost dose on treatment outcome in breast c o n s e r v i n g therapy C. Vrie/ing The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Depart. merit of Radiotherapy, Amsterdam, The Netherlands Two major endpoints of breast conserving therapy are good local control and good cosmetic outcome. A higher radiotherapy dose influences local control positively, while affecting cosmesis negatively. Little is known about the radiotherapy dose that gives an optimal balance between the two endpoints, The B-06 trial of the National Surgical Adjuvant Breast and Bowel Project demonstrated that whole breast irradiation (WBI) with a dose of 50 Gy in patients with tumor-free specimen margins, reduced the local recurrence rate at 12 years from 35 to 10%. Others claimed that omitting the local boost resulted in local control rates comparable to those of other institutions that routinely used a boost. The Lyon trial, randomizing 1024 patients between a 10-Gy boost (given in fractions of 2.5 Gy) to the tumor area or no further treatment after WBI of 50 Gy showed that the boost significantly reduced the risk of early local recurrence in patients with tumor-free margins from 4.5% to 3.6% at 5 years. Is this statistically significant difference in local control clinically relevant enough to give all patients a boost? The "boost versus no boost trial" of the European Organization for Research and Treatment of Cancer (EORTC) showed that in patients with a microscopically complete resection treated with a whole breast irradiation of 50 Gy, a 16-Gy boost could reduce the 5-year actuarial recurrence rate from 6.8% to 4.3% (p < 0.0001). The largest clinical benefit of the boost was observed in patients younger than 40 years of age; at 5 years the local recurrence rate was reduced from 19.5% to 10.2% (p = 0.002). For patients aged 41 to 50 the local recurrence rate was reduced from 9.5% to 5.8% (p = 0.02) and for patients older than 50 years from 4.1% to 3.0% (p = 0.1). In a subgroupanalysis of patients older than 50 years of age, no subgroups could be defined who might significantly benefit from the boost dose. The influence of the radiation dose on cosmetic outcome has been subject of many studies. Some studies, including the Lyon trial, concluded that a boost dose had no effect on the cosmetic outcome, in terms of the degree of breast retraction or the proportion of patients having an excellent or good cosmetic result, although patients treated with a boost may have had an increased frequency of telangiectasia. In the EORTC boost study, the boost affected the cosmetic outcome negatively according to the panel assessment: the cosmetic result at 3 years was excellent or good in 86% of the noboost group compared to 71% in the boost group. Other treatment=related factors that influenced cosmesis negatively were a large excision volume and the presence of breast complications (infection and/or hematoma), It can be concluded that especially for patients younger than 50 years of age treated with BCT the radiotherapy boost is an essential part of the treatment, despite the negative effect of the boost on cosmesis. Thus far, the influence of the boost on local control for patients older than 50 years of age seems limited, although longer follow-up is needed before definite conclusions can be reached, 8
Invited
Localised treatment In breast cancer: intraoperative radiation therapy (IORT) R. Orecchia European Institute of Onco/ogy, Radiotherapy Departament, Milan, Italy Today, the standard conservative treatment for early-stage breast cancer consists of complete surgical resection ~of the primary tumour, axillary dissection or sentinel node biopsy and postoperative irradiation of the remaining breast. Debate still exists about the optimal minimum treatment required for adequate local control without compromising the therapeutic effect when the risk is significantly lower (as occurred in patients with old age, T2 tumour below 25 ram, etc). Among the most critical endpoints are the avoidance of
unnecessary side-effects and conversely the shortening of the overall treatment time thus improving the quality of life. We have focused our interest on the use of Intraoperative Radiation Therapy (IORT). This technique has demonstrated its capacity for safely delivering relatively high single doses of irradiation directly to the tumor bed at the time of an operation while sparing adjacent normal surrounding tissues. The use of IORT as the sole modality of irradiation has the potential for accurately treating the tumour bed since the applicator can safely be placed under the direct visual control into the open surgical field. The skin and the subcutaneous tissue are not irradiated, thus decreasing the potential risk of fibrosis and eventually obtaining a better cosmesis. A prospective randomised study, called ELectron Intra Operative Therapy (ELIOT), started in December 2000 comparing standard external beam irradiation (50 Gy on the whole breast and 10 Gy boost on tumour bed) with a single dose (21 Gy at 90% isodose) of intraoperative irradiation on a limited field, in order to evaluate effectiveness of the new approach in terms of local control, regional control, disease-free, distant metastases and overall survival, cosmetic outcome and cost. This study is expected to finish in 3 years, during the first sixteen months 235 patients were included. The IORT treatment has been very well accepted by all patients both,due to the rapidity of the radiation course in case of IORT as a whole treatment and to the shortening of the subsequent external radiotherapy in case of IORT as an anticipated boost. We believe that single dose intraoperative radiotherapy after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy, which deserves further clinical evaluation through large-scale randomised tdals. 9
Invited
Intra-operative (contra) G Ross Royal Marsden Hospital, Department of Radiotherapy, London, United Kingdom Abstract not received
WHY IS RT G O O D F O R PALLIATION 10
Invited
Can radiotherapy improve breathlessness in patients with lung cancer? F.R. Macbeth VelindreNHS TRUST, Cardiff, Wales, United Kingdom Breathlessness is one of the commoner symptoms in patients with locally advanced lung cancer, occurring in up to 50% of patients at presentation. In randomised trials of palliative external beam thoracic radiotherapy (TRT) for patients with non-small cell lung cancer, there is good evidence that breathlessness can be palliated in a proportion of patients, but that the effect is usually less than on cough, haemoptysis and chest pain. In studies of patients treated with endobronchial radiotherapy, there are also reports of significant improvement But again, this is not in all patients and less marked than for other symptoms. Why should this be? Breathlessness is a subjective symptom and difficult to measure reliably, and in patients with lung cancer may be multi-factorial. Most patients have a background of chronic airways disease, and a proportion also have ischaemic heart disease and heart failure. Pleural or pericardial effusions, diffuse interstitial tumour growth (e.g. bronchio=alveolar carcinoma), a large space occupying tumour mass or multiple lung metastases can all cause breathlessness. It is only when a tumour is causing obstruction of a major airway (with or without atelectasis) is it likely that TRT will produce an improvement. Finally the effects of radiation fibrosis may, in longer survivors, compromise lung function. So it is perhaps not surprising that only some patients get significant and sustained improvement in this distressing symptom.
Wednesday, 18 September 2002
Symposia HOW TO MANAGE EARLY BREAST CANCER ? 7
Invited
The impact o f a boost dose on treatment outcome in breast c o n s e r v i n g therapy C. Vrie/ing The Netherlands Cancer Institute, Antoni van Leeuwenhoekhuis, Depart. merit of Radiotherapy, Amsterdam, The Netherlands Two major endpoints of breast conserving therapy are good local control and good cosmetic outcome. A higher radiotherapy dose influences local control positively, while affecting cosmesis negatively. Little is known about the radiotherapy dose that gives an optimal balance between the two endpoints, The B-06 trial of the National Surgical Adjuvant Breast and Bowel Project demonstrated that whole breast irradiation (WBI) with a dose of 50 Gy in patients with tumor-free specimen margins, reduced the local recurrence rate at 12 years from 35 to 10%. Others claimed that omitting the local boost resulted in local control rates comparable to those of other institutions that routinely used a boost. The Lyon trial, randomizing 1024 patients between a 10-Gy boost (given in fractions of 2.5 Gy) to the tumor area or no further treatment after WBI of 50 Gy showed that the boost significantly reduced the risk of early local recurrence in patients with tumor-free margins from 4.5% to 3.6% at 5 years. Is this statistically significant difference in local control clinically relevant enough to give all patients a boost? The "boost versus no boost trial" of the European Organization for Research and Treatment of Cancer (EORTC) showed that in patients with a microscopically complete resection treated with a whole breast irradiation of 50 Gy, a 16-Gy boost could reduce the 5-year actuarial recurrence rate from 6.8% to 4.3% (p < 0.0001). The largest clinical benefit of the boost was observed in patients younger than 40 years of age; at 5 years the local recurrence rate was reduced from 19.5% to 10.2% (p = 0.002). For patients aged 41 to 50 the local recurrence rate was reduced from 9.5% to 5.8% (p = 0.02) and for patients older than 50 years from 4.1% to 3.0% (p = 0.1). In a subgroupanalysis of patients older than 50 years of age, no subgroups could be defined who might significantly benefit from the boost dose. The influence of the radiation dose on cosmetic outcome has been subject of many studies. Some studies, including the Lyon trial, concluded that a boost dose had no effect on the cosmetic outcome, in terms of the degree of breast retraction or the proportion of patients having an excellent or good cosmetic result, although patients treated with a boost may have had an increased frequency of telangiectasia. In the EORTC boost study, the boost affected the cosmetic outcome negatively according to the panel assessment: the cosmetic result at 3 years was excellent or good in 86% of the noboost group compared to 71% in the boost group. Other treatment=related factors that influenced cosmesis negatively were a large excision volume and the presence of breast complications (infection and/or hematoma), It can be concluded that especially for patients younger than 50 years of age treated with BCT the radiotherapy boost is an essential part of the treatment, despite the negative effect of the boost on cosmesis. Thus far, the influence of the boost on local control for patients older than 50 years of age seems limited, although longer follow-up is needed before definite conclusions can be reached, 8
Invited
Localised treatment In breast cancer: intraoperative radiation therapy (IORT) R. Orecchia European Institute of Onco/ogy, Radiotherapy Departament, Milan, Italy Today, the standard conservative treatment for early-stage breast cancer consists of complete surgical resection ~of the primary tumour, axillary dissection or sentinel node biopsy and postoperative irradiation of the remaining breast. Debate still exists about the optimal minimum treatment required for adequate local control without compromising the therapeutic effect when the risk is significantly lower (as occurred in patients with old age, T2 tumour below 25 ram, etc). Among the most critical endpoints are the avoidance of
unnecessary side-effects and conversely the shortening of the overall treatment time thus improving the quality of life. We have focused our interest on the use of Intraoperative Radiation Therapy (IORT). This technique has demonstrated its capacity for safely delivering relatively high single doses of irradiation directly to the tumor bed at the time of an operation while sparing adjacent normal surrounding tissues. The use of IORT as the sole modality of irradiation has the potential for accurately treating the tumour bed since the applicator can safely be placed under the direct visual control into the open surgical field. The skin and the subcutaneous tissue are not irradiated, thus decreasing the potential risk of fibrosis and eventually obtaining a better cosmesis. A prospective randomised study, called ELectron Intra Operative Therapy (ELIOT), started in December 2000 comparing standard external beam irradiation (50 Gy on the whole breast and 10 Gy boost on tumour bed) with a single dose (21 Gy at 90% isodose) of intraoperative irradiation on a limited field, in order to evaluate effectiveness of the new approach in terms of local control, regional control, disease-free, distant metastases and overall survival, cosmetic outcome and cost. This study is expected to finish in 3 years, during the first sixteen months 235 patients were included. The IORT treatment has been very well accepted by all patients both,due to the rapidity of the radiation course in case of IORT as a whole treatment and to the shortening of the subsequent external radiotherapy in case of IORT as an anticipated boost. We believe that single dose intraoperative radiotherapy after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy, which deserves further clinical evaluation through large-scale randomised tdals. 9
Invited
Intra-operative (contra) G Ross Royal Marsden Hospital, Department of Radiotherapy, London, United Kingdom Abstract not received
WHY IS RT G O O D F O R PALLIATION 10
Invited
Can radiotherapy improve breathlessness in patients with lung cancer? F.R. Macbeth VelindreNHS TRUST, Cardiff, Wales, United Kingdom Breathlessness is one of the commoner symptoms in patients with locally advanced lung cancer, occurring in up to 50% of patients at presentation. In randomised trials of palliative external beam thoracic radiotherapy (TRT) for patients with non-small cell lung cancer, there is good evidence that breathlessness can be palliated in a proportion of patients, but that the effect is usually less than on cough, haemoptysis and chest pain. In studies of patients treated with endobronchial radiotherapy, there are also reports of significant improvement But again, this is not in all patients and less marked than for other symptoms. Why should this be? Breathlessness is a subjective symptom and difficult to measure reliably, and in patients with lung cancer may be multi-factorial. Most patients have a background of chronic airways disease, and a proportion also have ischaemic heart disease and heart failure. Pleural or pericardial effusions, diffuse interstitial tumour growth (e.g. bronchio=alveolar carcinoma), a large space occupying tumour mass or multiple lung metastases can all cause breathlessness. It is only when a tumour is causing obstruction of a major airway (with or without atelectasis) is it likely that TRT will produce an improvement. Finally the effects of radiation fibrosis may, in longer survivors, compromise lung function. So it is perhaps not surprising that only some patients get significant and sustained improvement in this distressing symptom.