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554 poster Treating local recurrences after conservative treatment for breast cancer: a non-randomized comparison between second conservative treatment and mastectomy
Posters
$245
residual cancer cells might move centripetally with its collapse. If fluid is replaced by organised tissue, however, the final site of any residual cancer cells is less clear. CT imaging with clips is becoming gold standard for target Iocalisation in breast, several studies highlighting the inaccuracies of clinical assessment. In one study, homogeneous versus heterogeneous appearance, surgeryto-scan interval and cavity size have been linked to clarity of image, but all cavity volumes decreased in time [1]. Another study reported shrinkage by 33% over 28 days [2]. A C T study [3] noted that surgical clips did not always match the perceived post-operative cavity: there are other reports of clips migration. In sites where soft tissue discrimination is of importance, such as prostate and brain, MR planning is established and could aid understanding of the natural history of the Target in the breast. Methods: Using Open MRI, scanning in the treatment position, over 1000 breast cancer patients have had MRtargeted radiotherapy planning. In a retrospective, randomly selected group of 30 post-WLE patients, the appearance of the post-surgical cavity was assessed in 3 dimensions. Results: Median time between surgery and scanning was 48 (range 28-234) days. All but 5/30 (17%) cases showed some degree of image inhomogeneity of the cavity: 26/30 (87%) were described as complex and cystic, and apparent concentric rings of varying signal were seen in 3/30 (10%). If a CTV of 15mm were chosen, assuming the apparent cavity to be hollow, 14/30 cases (47%) would have had part of a CTV of 15mm receiving less than 50% of the prescribed dose. Conclusion: MRI demonstrates complex cavities and changes that might indicate healing. Such healing may lead to movement of any surgical clips or other visible markers, and also to the position of any residual cancer cells. Further studies are needed.
[1] Snlitt et al (2000) Breast electron boost planning: comparison of CT and US.Radiology 2001:219:203-6 [2] Bentel G et al (1999) Variability of the location of IMV and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning In J Radiat Oncol Biol Phys 44:1017-1025 [3] Weed D et al (2003) The validity of clips as a radiographic surrogate for the biopsy cavity in image-guided accelerated partial breast irradiation Int J Radiat Oncol Biol Phys 57:$308 553 poster Hyperthermia in addition to re-irradiation cancer: 4 or 8 treatments?
for breast
J. van Der Zee 1, J.W. Mens 2, W.J. Graveland3, E.M. Verloopvan 't Hof ~, G.g. van Rhoon ~ ~Erasmus MC, Radiation Oncology, Hyperthermia Unit, Rotterdam, The Netherlands 2Erasmus MC, Radiation Oncology, Rotterdam, The Netherlands 3Erasmus MC, Statistics, Rotterdam, The Netherlands Introduction: Addition of hyperthermia to re-irradiation in patients with breast cancer doubles the complete response rate. The optimum number of hyperthermia treatments is unknown. In t996, we were facing the problem of inadequate capacity for hyperthermia applied after each radiation fraction, which was until then the standard treatment schedule. Published results from randomized studies, comparing a low with a high number of hyperthermia treatments in addition to radiotherapy, had showed no differences in complete response rate. The number of patients was too low to start a randomized study. It was
decided to continue with 4 hyperthermia treatments and to evaluate treatment outcome in comparison to historical controls treated 8 times (in the period 1992-1996, and published results in 107 patients treated before 1992 (Br. J. Cancer 1999;79:483-490)). Materials and methods: Of 125 patients, treated with reirradiation and hyperthermia in the period October 1992 January 2000, sufficient information was available for this first evaluation. Fifty-four patients were scheduled to 8 and 71 patients to 4 hyperthermia treatments. Results: All patients received 8 fractions of 4 Gy and 123 patients received the planned number of hyperthermia treatments. In 48 patients treated for microscopic disease, local control till death or date of last follow-up was achieved in 77%, not significantly different from our published results (83%). Following 8 hyperthermia treatments (17 pts) this was 65% and following 4 treatments 84% (n.s.). For patients with a maximum turnout diameter smaller than 3 cm, complete response rate was 83%, not significantly different from the 87% published in 1999. CR rate was 83% following 8 and 82% following 4 hyperthermia treatments. For patients with tumours with a maximum diameter larger than 3 cm, complete response was achieved in 54%, which is not significantly different from the published 65%. CR rate was 44% following 8 and 65% following 4 hyperthermia treatments. Conclusion: Local control in patients treated for microscopic disease and complete response rate in patients treated for macroscopic disease following 4 hyperthermia treatments is as good as following 8 hyperthermia treatments.
554 poster Treating local recurrences after conservative treatment for breast cancer: a non-randomized comparison between second conservative treatment and mastectomy
B. Guix~ J. Lejarcegui, J. Tel/o, G. Zanon, H. Palombo, J. De/ Campo, D. Rubio, P. Palombo Fundacio IMOR, Medical Institute for Radiotherapy, Radiotherapy, Barcelona, Spain Aim of the study: To report the long term results obtained in a prospective group of patients treated for local recurrence after conservative treatment of breast cancer treated by second conservative surgery and brachytherapy or total mastectomy. Methods: Between 12/1990 and 04/2002, 79 patients with local recurrence after conservative treatment for breast cancer were offered total mastectomy as salvage treatment. 43 of them refused mastectomy and were treated by a second lumpectomy followed by HDR brachytherapy implant to the tumor bed plus a 3 cm safety margin. Brachytherapy was given between 1 and 3 weeks after excision. Implants were done at the time of surgery in 37 cases and in the remaining 6 patients at the time of beginning treatment. The average number of implanted tubes was 7 (range 4-11) and the average volume of the reference isodose curve was 56 cc. HDR brachytherapy doses were 30 Gy in 12 fractions in 5 days. Patients treated by mastectomy had no further radiotherapy treatment.
Patients with positive oestrogen receptors were treated with tamoxifen for 2-5 years, premenopausal patients with negative receptors had chemotherapy and postmenopausal patients with negative receptors had no systemic treatment. No patient was lost for follow-up. Special attention to local, regional or distant recurrence, survival, fibrosis, late effects and cosmesis was done during the follow*up period.
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Results: All patients completed treatment. During the 12year, 1-year minimum follow-up, there were 8 patients who had regional (2 cases) or distant metastases (6 cases) as their first site of failure. Three of them experienced a differed local recurrence and 1 of them died from the disease. Actuarial results at 12-year were: local control 84.2 %; disease free survival 65.4 %; and survival 90.7 %. Cosmetic results were satisfactory in 89.4 %. No patient experienced arm edema or grade 3-4 early or late complications. Between the 12 patients that were followed-up for at least 10-years, 10 of them were with their breast still in place at 10-year. Conclusions: HDR brachytherapy was a safe and effective method of treatment for small-size, low-risk, local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of HDR brachytherapy given in 12 fractions along 5 days at 2.5 Gy/fraction, 2-3 times every day was safe in patients previously treated. The good results achieved justifies the initiation of randomized trials exploring its use as standard treatment in selected patients with low-risk recurrent breast tumors. 555 poster An Italian Society of Radiation Oncology (AIRO) survey: radiotherapy after breast conservative treatment (BCT) for early-stage breast cancer
C. Aristei 1, M. Amichetti 2, L. Nardone ~, C. Vidal[~ IPoliclinico Monteluce, Radiation Oncology, Perugia, Italy 2Cagliari Hospital, Italy 3Roma University, (UCSC), Rome, Italy 4Trieste Hospital, Trieste, Italy Purpose: To survey current practices after conservative surgery in early-stage breast cancer patients in Italy and the adherence to national and international guidelines. Methods: A current practice questionnaire was sent to the 138 Italian Radiotherapy (RT) Departments (Dpts) in 2002; 66 Centres (48%) responded. Results: The survey found that BCT is performed when tumour size is -< 3 cm at 50 institutions. If margins are positive, re-excision is done at 52 centres, at the remaining 14, or in the case of positive margins following re-excision, mastectomy is performed at 20 institutions, a higher boost dose is employed at 31, standard approach is not modified at 6, a boost is given at 6 centres that otherwise do not use it routinely, and boost is given with brachytherapy at 3. The presence of an extensive intraductal component does not change the treatment approach at 44 centres. The median interval between surgery and RT is 60 days (range 30-180). Adjuvant chemotherapy (CT) is preferably administered concurrently with RT at 23 centres, after RT at 9, before RT at 26, while a sandwich treatment (CT-RT-CT) is used at 8. Regional lymph nodes (LNs) are never irradiated at 10 institutions, at the others the choice for RT depends on the number of positive LNs and/or involvement of axillary fat and/or location of tumour in medial quadrants. Supraclavicular, axillary, and internal mammary nodes are treated at 21, 45 and 27 Dpts respectively. Standard fractionation is used at all centres but 5, where hypofractionation is employed with a dose per fraction of 2.25-2.75 Gy. 4-6 MV x-rays are used at 60 institutions. Boost dose is 10 Gy at 59 centres though it can go higher (14 to 20 Gy) if margins are not negative. Boost is generally given with external beam RT, electrons are mainly employed. An immobilization device is always used at 33 centres. CTV is delineated on CT slides at 57, tangential fields are simulated at 62, and films are stored at 59. Computerized treatment planning is carried out at 59 centres, dose is prescribed at ICRU point at 56. Portal films are
Posters
routinely taken at 54 centres. Both acute and late side effects and cosmesis are evaluated at 65, 64 and 58 centres respectively. Conclusions: The quality of RT delivery has improved in Italy since the publication of AIRO Guidelines in 1997 and of the patterns of care in North-Italy (Radiother Onco151: 79-85, 1999). Overall, significant differences are related to both approaches according to margin status and radiation treatment of draining LNs. These latter topics will be discussed in the next published guidelines. 556 poster Radiation to internal mammary nodes in breast cancer patients with medial lesions: is there a benefit for survival?
G. Grabenbauer, A. Ernst-Stecken, A. Hartanto Tulusan, R. Sauer University of Erlangen, Radiation Oncology, Erlangen, Germany Background: according to recent data provided by Lohrish et al. (J Clin Oncol 2000; 18: 2828-35) medial location of early breast cancer was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral location. Five-year systemic disease-free survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (p<.005). Corresponding 5-year disease-specific survival rates were 75.7% and 80.8%, respectively (p<.03). The two-fold risk of relapse and breast cancer death associated with high-risk medial breast tumours may be due to occult spread to internal mammary nodes (IMN). Purpose: to explore the prognostic impact of radiation therapy (RT) to IMN in early breast cancer patients with medial hemisphere tumour location and to compare 10-yearoverall survival (OS) and systemic 10-year-disease-free survival rates (SDF) with patients (pts) treated for laterally located breast cancer without RT to IMN. Patients and methods: Between 1985 and 1996, a total of 872 patients (492 pts had lateral and 330 pts medial lesions) with early breast cancer were treated by surgery and postoperative RT with or without chemotherapy. Prognostic factors including T-, N-category, grading, receptor status were equally distributed between the two groups. All pts with medial lesions received RT to IMN by a mixed beam approach (50% photons, 50% electrons) with a total dose of 50 Gy and single daily fractions of 2 Gy. In pts with lateral lesions RT was directed to the breast alone (50.4 Gy total dose, Boost 12-16 Gy, single fraction 1.8 Gy), only with positive axillary nodes IMN were treated Results: for all 872 pts, OS and SDF rates at 10 years were 61.5% and 67.4%, respectively. OS for lateral lesions and medial lesions was 60% and 64%, SDF for lateral and medial tumours 65.5% and 70.1%, respectively. Subgroup analysis is given in table 1. Remarkably, no subgroup could be identified in which prognosis of pts with medial tumours was inferior to survival data for pts with lateral lesions. In postmenopausal pts, OS was significantly better for pts with medial vs. lateral tumours (58.9% vs. 52%, p=0.05), in pts receiving adjuvant chemotherapy SDF was better for with medial vs. lateral tumours (67.5% vs. 54.5%, p=0.02).
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residual cancer cells might move centripetally with its collapse. If fluid is replaced by organised tissue, however, the final site of any residual cancer cells is less clear. CT imaging with clips is becoming gold standard for target Iocalisation in breast, several studies highlighting the inaccuracies of clinical assessment. In one study, homogeneous versus heterogeneous appearance, surgeryto-scan interval and cavity size have been linked to clarity of image, but all cavity volumes decreased in time [1]. Another study reported shrinkage by 33% over 28 days [2]. A C T study [3] noted that surgical clips did not always match the perceived post-operative cavity: there are other reports of clips migration. In sites where soft tissue discrimination is of importance, such as prostate and brain, MR planning is established and could aid understanding of the natural history of the Target in the breast. Methods: Using Open MRI, scanning in the treatment position, over 1000 breast cancer patients have had MRtargeted radiotherapy planning. In a retrospective, randomly selected group of 30 post-WLE patients, the appearance of the post-surgical cavity was assessed in 3 dimensions. Results: Median time between surgery and scanning was 48 (range 28-234) days. All but 5/30 (17%) cases showed some degree of image inhomogeneity of the cavity: 26/30 (87%) were described as complex and cystic, and apparent concentric rings of varying signal were seen in 3/30 (10%). If a CTV of 15mm were chosen, assuming the apparent cavity to be hollow, 14/30 cases (47%) would have had part of a CTV of 15mm receiving less than 50% of the prescribed dose. Conclusion: MRI demonstrates complex cavities and changes that might indicate healing. Such healing may lead to movement of any surgical clips or other visible markers, and also to the position of any residual cancer cells. Further studies are needed.
[1] Snlitt et al (2000) Breast electron boost planning: comparison of CT and US.Radiology 2001:219:203-6 [2] Bentel G et al (1999) Variability of the location of IMV and glandular breast tissue in breast cancer patients undergoing routine CT-based treatment planning In J Radiat Oncol Biol Phys 44:1017-1025 [3] Weed D et al (2003) The validity of clips as a radiographic surrogate for the biopsy cavity in image-guided accelerated partial breast irradiation Int J Radiat Oncol Biol Phys 57:$308 553 poster Hyperthermia in addition to re-irradiation cancer: 4 or 8 treatments?
for breast
J. van Der Zee 1, J.W. Mens 2, W.J. Graveland3, E.M. Verloopvan 't Hof ~, G.g. van Rhoon ~ ~Erasmus MC, Radiation Oncology, Hyperthermia Unit, Rotterdam, The Netherlands 2Erasmus MC, Radiation Oncology, Rotterdam, The Netherlands 3Erasmus MC, Statistics, Rotterdam, The Netherlands Introduction: Addition of hyperthermia to re-irradiation in patients with breast cancer doubles the complete response rate. The optimum number of hyperthermia treatments is unknown. In t996, we were facing the problem of inadequate capacity for hyperthermia applied after each radiation fraction, which was until then the standard treatment schedule. Published results from randomized studies, comparing a low with a high number of hyperthermia treatments in addition to radiotherapy, had showed no differences in complete response rate. The number of patients was too low to start a randomized study. It was
decided to continue with 4 hyperthermia treatments and to evaluate treatment outcome in comparison to historical controls treated 8 times (in the period 1992-1996, and published results in 107 patients treated before 1992 (Br. J. Cancer 1999;79:483-490)). Materials and methods: Of 125 patients, treated with reirradiation and hyperthermia in the period October 1992 January 2000, sufficient information was available for this first evaluation. Fifty-four patients were scheduled to 8 and 71 patients to 4 hyperthermia treatments. Results: All patients received 8 fractions of 4 Gy and 123 patients received the planned number of hyperthermia treatments. In 48 patients treated for microscopic disease, local control till death or date of last follow-up was achieved in 77%, not significantly different from our published results (83%). Following 8 hyperthermia treatments (17 pts) this was 65% and following 4 treatments 84% (n.s.). For patients with a maximum turnout diameter smaller than 3 cm, complete response rate was 83%, not significantly different from the 87% published in 1999. CR rate was 83% following 8 and 82% following 4 hyperthermia treatments. For patients with tumours with a maximum diameter larger than 3 cm, complete response was achieved in 54%, which is not significantly different from the published 65%. CR rate was 44% following 8 and 65% following 4 hyperthermia treatments. Conclusion: Local control in patients treated for microscopic disease and complete response rate in patients treated for macroscopic disease following 4 hyperthermia treatments is as good as following 8 hyperthermia treatments.
554 poster Treating local recurrences after conservative treatment for breast cancer: a non-randomized comparison between second conservative treatment and mastectomy
B. Guix~ J. Lejarcegui, J. Tel/o, G. Zanon, H. Palombo, J. De/ Campo, D. Rubio, P. Palombo Fundacio IMOR, Medical Institute for Radiotherapy, Radiotherapy, Barcelona, Spain Aim of the study: To report the long term results obtained in a prospective group of patients treated for local recurrence after conservative treatment of breast cancer treated by second conservative surgery and brachytherapy or total mastectomy. Methods: Between 12/1990 and 04/2002, 79 patients with local recurrence after conservative treatment for breast cancer were offered total mastectomy as salvage treatment. 43 of them refused mastectomy and were treated by a second lumpectomy followed by HDR brachytherapy implant to the tumor bed plus a 3 cm safety margin. Brachytherapy was given between 1 and 3 weeks after excision. Implants were done at the time of surgery in 37 cases and in the remaining 6 patients at the time of beginning treatment. The average number of implanted tubes was 7 (range 4-11) and the average volume of the reference isodose curve was 56 cc. HDR brachytherapy doses were 30 Gy in 12 fractions in 5 days. Patients treated by mastectomy had no further radiotherapy treatment.
Patients with positive oestrogen receptors were treated with tamoxifen for 2-5 years, premenopausal patients with negative receptors had chemotherapy and postmenopausal patients with negative receptors had no systemic treatment. No patient was lost for follow-up. Special attention to local, regional or distant recurrence, survival, fibrosis, late effects and cosmesis was done during the follow*up period.
$246
Results: All patients completed treatment. During the 12year, 1-year minimum follow-up, there were 8 patients who had regional (2 cases) or distant metastases (6 cases) as their first site of failure. Three of them experienced a differed local recurrence and 1 of them died from the disease. Actuarial results at 12-year were: local control 84.2 %; disease free survival 65.4 %; and survival 90.7 %. Cosmetic results were satisfactory in 89.4 %. No patient experienced arm edema or grade 3-4 early or late complications. Between the 12 patients that were followed-up for at least 10-years, 10 of them were with their breast still in place at 10-year. Conclusions: HDR brachytherapy was a safe and effective method of treatment for small-size, low-risk, local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of HDR brachytherapy given in 12 fractions along 5 days at 2.5 Gy/fraction, 2-3 times every day was safe in patients previously treated. The good results achieved justifies the initiation of randomized trials exploring its use as standard treatment in selected patients with low-risk recurrent breast tumors. 555 poster An Italian Society of Radiation Oncology (AIRO) survey: radiotherapy after breast conservative treatment (BCT) for early-stage breast cancer
C. Aristei 1, M. Amichetti 2, L. Nardone ~, C. Vidal[~ IPoliclinico Monteluce, Radiation Oncology, Perugia, Italy 2Cagliari Hospital, Italy 3Roma University, (UCSC), Rome, Italy 4Trieste Hospital, Trieste, Italy Purpose: To survey current practices after conservative surgery in early-stage breast cancer patients in Italy and the adherence to national and international guidelines. Methods: A current practice questionnaire was sent to the 138 Italian Radiotherapy (RT) Departments (Dpts) in 2002; 66 Centres (48%) responded. Results: The survey found that BCT is performed when tumour size is -< 3 cm at 50 institutions. If margins are positive, re-excision is done at 52 centres, at the remaining 14, or in the case of positive margins following re-excision, mastectomy is performed at 20 institutions, a higher boost dose is employed at 31, standard approach is not modified at 6, a boost is given at 6 centres that otherwise do not use it routinely, and boost is given with brachytherapy at 3. The presence of an extensive intraductal component does not change the treatment approach at 44 centres. The median interval between surgery and RT is 60 days (range 30-180). Adjuvant chemotherapy (CT) is preferably administered concurrently with RT at 23 centres, after RT at 9, before RT at 26, while a sandwich treatment (CT-RT-CT) is used at 8. Regional lymph nodes (LNs) are never irradiated at 10 institutions, at the others the choice for RT depends on the number of positive LNs and/or involvement of axillary fat and/or location of tumour in medial quadrants. Supraclavicular, axillary, and internal mammary nodes are treated at 21, 45 and 27 Dpts respectively. Standard fractionation is used at all centres but 5, where hypofractionation is employed with a dose per fraction of 2.25-2.75 Gy. 4-6 MV x-rays are used at 60 institutions. Boost dose is 10 Gy at 59 centres though it can go higher (14 to 20 Gy) if margins are not negative. Boost is generally given with external beam RT, electrons are mainly employed. An immobilization device is always used at 33 centres. CTV is delineated on CT slides at 57, tangential fields are simulated at 62, and films are stored at 59. Computerized treatment planning is carried out at 59 centres, dose is prescribed at ICRU point at 56. Portal films are
Posters
routinely taken at 54 centres. Both acute and late side effects and cosmesis are evaluated at 65, 64 and 58 centres respectively. Conclusions: The quality of RT delivery has improved in Italy since the publication of AIRO Guidelines in 1997 and of the patterns of care in North-Italy (Radiother Onco151: 79-85, 1999). Overall, significant differences are related to both approaches according to margin status and radiation treatment of draining LNs. These latter topics will be discussed in the next published guidelines. 556 poster Radiation to internal mammary nodes in breast cancer patients with medial lesions: is there a benefit for survival?
G. Grabenbauer, A. Ernst-Stecken, A. Hartanto Tulusan, R. Sauer University of Erlangen, Radiation Oncology, Erlangen, Germany Background: according to recent data provided by Lohrish et al. (J Clin Oncol 2000; 18: 2828-35) medial location of early breast cancer was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral location. Five-year systemic disease-free survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (p<.005). Corresponding 5-year disease-specific survival rates were 75.7% and 80.8%, respectively (p<.03). The two-fold risk of relapse and breast cancer death associated with high-risk medial breast tumours may be due to occult spread to internal mammary nodes (IMN). Purpose: to explore the prognostic impact of radiation therapy (RT) to IMN in early breast cancer patients with medial hemisphere tumour location and to compare 10-yearoverall survival (OS) and systemic 10-year-disease-free survival rates (SDF) with patients (pts) treated for laterally located breast cancer without RT to IMN. Patients and methods: Between 1985 and 1996, a total of 872 patients (492 pts had lateral and 330 pts medial lesions) with early breast cancer were treated by surgery and postoperative RT with or without chemotherapy. Prognostic factors including T-, N-category, grading, receptor status were equally distributed between the two groups. All pts with medial lesions received RT to IMN by a mixed beam approach (50% photons, 50% electrons) with a total dose of 50 Gy and single daily fractions of 2 Gy. In pts with lateral lesions RT was directed to the breast alone (50.4 Gy total dose, Boost 12-16 Gy, single fraction 1.8 Gy), only with positive axillary nodes IMN were treated Results: for all 872 pts, OS and SDF rates at 10 years were 61.5% and 67.4%, respectively. OS for lateral lesions and medial lesions was 60% and 64%, SDF for lateral and medial tumours 65.5% and 70.1%, respectively. Subgroup analysis is given in table 1. Remarkably, no subgroup could be identified in which prognosis of pts with medial tumours was inferior to survival data for pts with lateral lesions. In postmenopausal pts, OS was significantly better for pts with medial vs. lateral tumours (58.9% vs. 52%, p=0.05), in pts receiving adjuvant chemotherapy SDF was better for with medial vs. lateral tumours (67.5% vs. 54.5%, p=0.02).