- Email: [email protected]
409 Poster A dosimetric and treatment planning comparison between brachytherapy and single field electrons for breast boost irradiation
Posters
Wednesday/Thursday, 18-19 September 2002 S 135
established for patients with different TGF-~I genotypes. Results: The TGF-~I codon 25 Arg/Arg genotype was identified in 33 patients and Arg/Pro was identified in 8 patients. Dose-response curves for these two groups differed from each other with an enhancement ratio of 1,10 (95% CI 1,01-1,21) related to the Arg/Pro genotype. No association was observed between TGF-61 codon 25 genotype and acute reactions, nor was any association found between the two other assessed polymerphisms and any type of normal tissue reaction. Conclusion: Our data indicate that the TGF-131 codon 25 Arg/Pro genotype increases risk of radiation-induced subcutaneous fibrosis. However, our data are inconsistentwith previous findings suggesting that the Pro haplotype in codon 25 is associated with tower levels of circulating TGF-6 1 and decreased risk of different fibrotic disorders. This may be a reflection of the complexity and context dependency often being related to cytokine systerns, in order to confirm our result, we intend to apply the analysis to the remaining patents in the historic cohort. This study will be based on DNA isolated from histological archive material (formalin fixed, paraffin embedded sections of non-metastatic axillary lymph nodes or other normal tissue). 406
Poster
Radiotherapy and immediate breast reconstruction using i/e expander following mastectomy for breast cancer A. Richard Taller 1, N. Salem 1, P. Ananian 2, L. Gonzague Casablanca 1, V. Moutardiet 2, B. Lelong2, J. Guiramand2, S. Arnaud 2, R. Zalta2, G. Houvenaeghel2 1paoli Calmettes, Radiotherapy, Marseille, France 2paofi Calmettes, Surgery, Marseille, France Purpose: To assess the toxicity of radiotherapy associated with immediate breast reconstruction (IBR) using tissue expander and implant. Cosmetic results were also evaluated as second criteria, Methods and materials: From January 1999 to December 2000, all patients undergoing IBR using an expander/implant were retrospectively evaluated with respect to complications, rate of reconstruction failure, time for adjuvant treatment and aesthetic results. The majority of patients received also radiotherapy, most of them after reconstruction. Evaluation of complications was obtained by review of the patient chart, and aesthetic results were assessed with subjective self-assessment of patient satisfaction, Results: Seventy eight patients underwent mastectomy and IBR using an expander/implant. Fifty six (72%) received also radiotherapy either before or after reconstruction. The median dose delivered to the reconstructed breast (or the chest wall) was 50 Gy (45-60 Gy), including boost, in 2 Gy fractions. The median follow-up was twenty months (range 14-25 months), Complications were observed in 39.7 percent of cases and appeared correlated with radiotherapy (14% for non irradiated patients; 52% for irradiated patients; p=0.0001). Breast reconstruction failure was observed in 22 percent of cases and was not significantly dependant with irradiation (27% for irradiated patients vs 9% without irradiation; p=0.12). Tamoxifene (TMX) was not correlated with complications (43% with TMX vs 34% without; p=0.47), nor for breast reconstruction failure (19% with TMX and 24% without, p=0.6). Chemotherapy was correlated with higher complications and with significantly higher breast reconstruction failure (51% vs 27% (p=0.029) and. 34% vs 8% (p=0.012), respectively). Chemotherapy was never delayed. Self-assessment of patient satisfaction is ongoing, Conclusion : Immediate breast reconstruction using an expander/implant is safe and can be offered even when adjuvant treatment is required. Surgoons should be aware that complications and reconstruction failure rate are more frequent for patient undergoing post-implant radiotherapy. 407
Poster
Postmastectomy radiotherapy in 1-3 positive nodes J. Sa/inas 1, A. Pi~ero2, R. Garcia F3, M. De/as Heras 1 1Hospital Virgen de/a Arrixaca, Dept. of Radiotherapy, Murcia, Spain 2Hospita/Virgen de/a Arrixaca, Dept. of Surgery, Murcia, Spain 3Hospita/ Virgen de/a Arrixaca, Data Manager, Murcia, Spain Postmastectomy radiotherapy in breast carcinoma with 1-3 positives nodes remain a controversial issue. The impact on survival depend on reduce Ioco-regional relapse. Relapse rate in this population vary from 5 to 30% in majority of series, We analyze in our institution Ioco-regional relapse as first event in patients with breast carcinoma and the next criteria: completely excised by radical mastectomy and axilary dissection, free margins, pT1 or pT2 and one to three metastatic nodes. Between 1980 and 1969, 90 patients fulfilled the above criteria.
Characteristics of the patients and tumors were as follow (%): Age: mean 51 (23-88). Menopausal status: pro 47; post 53. Maximum diameter: mean: 2,87 cm (0.9-5). T-stage: T1 31,5; T2 68,5. Histology: ducta197. Histological differentiation: well 5; moderate 60; poorly 35. Necrosis 17. Vascular invasion 10. Number of isolated nodes: mean 10 (3-24). Number of affected nodes 1 : 41; 2: 30; 3: 29. Extracapsular extension 11. Adjuvant treatment: radiotherapy 7, chemotherapy 40 and hormonal therapy 26. Minimal follow-up were 10 years for patients alive. Results: Loco-regional relapse: 20/90: 22% (75% during the first three years) 10-yr Ioco-regional relapse free survival: 78,5 + 5% Univariant analysis (Cross-Tab: Chi-square, mantel-haenszel and fisher exact text; Kaplan-Meier: log-rank and breslow): age under 35 (37,5 vs. 21), premenopausal status (28,5 vs 16,5), poorly differentiated tumor (33 vs 21,5); T2 stage (29,5 vs 7); tumoral necrosis (50 vs 25) and vascular invasion (50 vs 27) showed higher rate of Ioco-regional relapse but only T-stage was statistically significative (p= 0.0201). Conclusion: The rate of Ioco-regional relapse in patients with 1-3 positve nodes is enough to preclude postoperative radiotherapy in spite of sistemic therapy. The low toxicity of modern radiotherapy appears to justify its use in all but individualized case iT1 stage, low grade, postmenopausal). The impact on survival will come from results of multinational randomized studies presently ongoing. 408
Poster
The radiotherapeutic management of breast cancer: a comparison between different european countries A. Taclhian, E. Ceilley, S. Goldberg, L. Grignon, L. Kachnic, S. Powell Massachusetts General Hospital, Radiation Oncology, Boston, U.S.A. Purpose: Compare the radiotherapeutic management of breast cancer in the different European countries. Methods: An international survey was sent to ESTRO members regarding their individual management of breast cancer. The results of 422 respondents from Europe are presented. For statistical analysis, the responses were grouped by countries as follows: France/Belgian (Fr.Bel)80 respondents, Germany/Austria/Switzerland (Ger.Au.Sw) 93, Italy 45, Spain/Portugal (Sp.Por) 50, Netherlands/Finland/Sweden/Denmark "North" 78, England/Scotland/Ireland (Eng.Sc.lr) 24 and Eastern Europe "East" 44 respondents. Results: Tumor Margins: Physicians were diverse in their definition of negative margins after lumpectomy for invasive cancers. Overall, 28% considered no tumor cells seen at the inked margins to be negative. This varied between 8% for Eng.Sc.lr and 46% for the North countries (p<0.001). 29% considered no tumor cells seen at <5 mm (range 38% for Eng.Sc.lr and 25% for East p<0.001). Post-mastectomy RT: There were significant differences in management techniques for patients after mastectomy. Overall, 84% of Europeans use post-mastectomy radiation (PMRT) in T3N0 lesions. This varied between 60% in Italy and 96% in Sp.Por. Only 67% in North used PMRT (p<0.01). In the 1-3 lymph node positive (LN+), 60% of European chose PMRT (range 19% in Italy and 74% in Sp.Por). In North countries 36% chose PMRT (p<0.001). In the >4LN+, 93% use PMRT varying between 88% and 97% with the exception of Italy where only 65% selected PMRT (p<0.01). 21% of respondents chose to treat the supraclavicular area (5% in Italy to 29% in Sp.Por, p<0.001) in T3N0, 41% (3% in Italy to 73% in Fr.Bel p<0.001) in 13 LN+ and 93% (63% in Eng.Sc.ir to 100% in North p<0.05) in >4 LN+. Regarding the axiila, 9.2% chose to use PMRT (0% in Italy and Eng.Sc.lr to 18% in East, p<0.0001) in T3N0, 14% (0% in Italy to 33% in East p<0.001) in 1-3 LN+ and in 53% (29% in Eng.Sc.lr to 81% in North p<0.05) in >4LN+. 10% chose to treat IMC (0% in Italy to 19% in Fr.Bei, p<0.001) in T3N0, 23% (0% in Italy to 49% in Fr.Bel p<0.01) in 1-3 LN positive, 35% (15% in Italy to 57% in FR.Bel p<0.01) in >4 LN+. Differences in regional RT after lumpectomy and DCIS will be presented. Conclusions: There are differences in the management of breast cancer between European countries. International surveys could lead to the design of prospective studies to define the optimal use of RT in the treatment of breast cancer. 409
Poster
A dosimetric and treatment planning comparison between brachytherapy and single field electrons for breast boost irradiation P. Ocamoo. P. Thirion, P. McCavana, A. Downes, S. Gdm/ey, J. Armstrong, C. Ke//y St. Luke's Hospita/, Physics, Dublin, ~re~and Introduction: Clear evidence for breast boost therapy is shown in a ran-
S 136 Wednesday/Thursday, 18-19 September 2002
domised EORTC trial (2288/10882) on patients who have undergone tumourectomy and whole breast irradiation. Choosing the optimum modality for the boost is a topical issue, and one of concern in the radiotherapy community, By using full 3D CT planning, this study compares the dosimetry and treatment planning characteristics of both HDR interstitial brachytherapy and electron beam radiotherapy for the delivery of a breast boost. Materials and Methods: This study is set out to accumulate 10 patients for technique comparison. Selection criteria were based on previous lumpectomy, whole breast EBRT and referral for HDR optimised brachytherapy. The subjects were CT scanned post implantation and images sent to PLATO BPS (brachytherapy planning system) and HELAX TMS (electron beam planning system). A matched Planning Target Volume (PTV) was then drawn. Dose Volume Histograms (DVH) were obtained for target volume, Organs at Risk (OAR) and implant. From this data, an assessment of the surface dose, PTV coverage, homogeneity of dose distribution and irradiation of organs at risk were then obtained, Results: Initial results indicate that a more homogenous dose distribution and higher coverage are obtained with electrons, if optimal selection of energy and applicator is carried out and that treatment is designed with the aid of CT planning. Brachytherapy on the other hand, provides a lower surface dose and a smaller treated volume of breast tissue. Dose to the OAR is within acceptable limits with both modalities but with is again indicated lower with_ electron treatments, Conclusions: Treatment planning analysis indicates significant differences between modalities. From the dosimetric point of view, electrons are indicared in cases where dose to the OAR's and good homogeneity are of more clinical import than dose to the surrounding breast tissue and cosmesis, 410 Poster T a r g e t e d intraoperative radiotherapy for breast cancer (Tar-
git): an international trial
J.S. Vaidya 1, D. Joseph2, B.S. Hilaris 3, J.S. Tobias 1, ,I. Houghton 1, M. Keshtgar 1, R. Sainsbury 1, L Taylor 1, M. Baum 1 1University College London, Surgery, London, UK 2Sir Charles Gairdner Hospital, Radiation Oncology, Nedlands, Australia 3New York Medical College, Radiation Oncology, New York, USA
Posters
411 Poster I n c r e a s e o f collagen
synthesis correlates with radiationinduced skin edema in breast cancer patients
Ft. Keskikuru 1, J. Nuutinen 1, A. Jukkola 2, V. Kataja 1, J. Risteli 3, T. Lahfi~1
1Kuopio University Hospital, Department of Oncology, Kuopio, Finland 20ulu University Hospital, Department of Oncology, Oulu, Finland 3University of Oulu, Department of.Medical Biochemistry, Oulu, Finland Purpose: Tissue hypoxia is related to the formation of tissue edema. Tissue hypoxia in the skin can be assessed by measuring the temporal variation of skin thickness after radiotherapy (RT). Variations of skin thickness were correlated with the marker of skin collagen synthesis in order to investigate their possible interrelationship. Material and Methods: Skin suction blisters were induced in irradiated and non-irradiated skin during RT and during follow-up (up to 2 years) in 21 breast cancer patients treated with breast conserving surgery and converttionally fractionated RT to 50 Gy. From skin suction,~blister fluid the procollagen concentration of type I collagen (PINP) was determined by a spesific radioimmunoassay. Concomitantly, the skin thickness was measured with a high frequency ultrasound (20 MHz). Results: Collagen synthesis starts to increase during RT while the skin thickness of the irradiated skin remains unchanged. The maximum level of the type I collagen synthesis was observed at 4 and 7 months postirradiation when also the skin thickness was markedly elevated. The correlation was statistically highly significant (p<0.005). After 7 months both the thickness of the irradiated skin and skin collagen synthesis declined to their protreatment levels during the follow-up period. Conclusion: We demonstrated significant changes both in skin thickness and collagen metabolism following conventionally fractionated RT in breast cancer patients. The results suggestthatthickeningof theskin is duetothe formation of skin edema and thus skin hypoxia which further stimulates collagen synthesis. 412 Poster T h e m e d i a l turnout location - An unfavourable prognostic fac-
tor (review of 1089 patients, 1984 - 1995) Breast conserving surgery followed by whole breast radiotherapy (including a tumour bed boost) is the current gold standard for operable breast cancer. However, symptomatic local recurrence occurs usually at the site of primary tumour, suggesting that it may be unnecessary to irradiate the whole breast. Also, it is estimated that up to 50% of local recurrence is attributable to 'geographical miss' by the boost dose. We have pioneered* the use of intra-operative radiotherapy delivered to the tumour bed under direct vision in a routine operation theatre using a novel portable radiotherapy device (Intrabeam, Pec) that delivers soft x-rays at 50Kv from the surface of a spherical applicator, which is available in various sizes and is inserted into the tumour bed after wide local excision of the turnout. The physical dose is 20Gy at the surface of the applicator and 5Gy at lcm depth. The estimated biologically effective dose at the surface is 50-120Gy, with a high therapeutic ratio between tumour bed and skin or lung dose. Cardiac protection is easily provided with a thin tungsten impregnated sheet on the posterior tumour bed, if on the left side. The pilot study in the UK using this technique (n=25) as a substitute for the boost was encouraging* - at a median follow up of 34 months no recurrences were reported and cosmetic appearance was good. The US (39) and the Australian (15) centres have treated 84 patients in local feasibility studies. We are embarking upon a multicentre randomised trial to test whether such an approach could replace the 6-wks of postoperative radiotherapy for infiltrating duct carcinoma. The UK centre has randomised 29 patients. Thus a total of 94 patients has been treated with the novel technique. The longest follow up is 45 months (median=18m). Our 3rd patient had skin necrosis due to the applicator surface being brought too close to it. The technique was modified and there has been no further toxicity. In the randomised UK patients there was one local recurrence at 22 months. This was a protocol violation; she had involved margins but did not have re-excision. Several centres in the USA, UK, Europe, India and Australasia are keen to participate in this trial. If proven, this approach could potentially save time, money and breasts both for hospitals and their patients. *Targeted intra-operative radiotherapy (Targit):An innovative method of treatment for early breast cancer JS VaJdya M Baum JS Tobias et al Ann Oncol 2001;12:1075-80
J. Hammer, C. Track, D.H. Seewa/d, K. Spieg/, ,1. Feichtinger Barmherzige Schwestern Hospital, Dept. of Radiotherapy, Linz, Austria Purpose: The authors report on the unfavourable results in survival and comesis in patients with medially located breast tumours (reed) compared to patients with cancer in the lateral quadrants (lat). Patients and Methods: From 1984 to 1995, 1089 patients with 1100 T1-2 N0-1 tumours were treated. 707 presented with lat, 294 with reed, and in 99 cases the primary tumour was located in the central region of the breast (centr). The prospective treatment method included breast conserving surgery and radiotherapy with 45 to 50 Gy to the whole breast. The internal mammary lymph node chain (IMC) was not electively irradiated. In 1025 patients a boost has been performed: 650 patients underwent an interstitial 10 Gy boost in 1 fraction, 375 an external beam boost (electrons or photons) and 75 had no boost. All axillary nodal positive patients underwent systemic therapy (6 x CMF or Tamoxifen). Mean follow up of survivors: 97 months (36 to 192 months). Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test. From 518 patients the cosmetic results were evaluated using a 4 grade scoring system. Results: Comparin~Tffed-and lat the actuarial survival parameters are highly significant in favour of the lateral turnouts (p-values: overall survival 0.025, disease specific survival 0.025, disease free rate 0.011). No significance is given in local oontrol (p = 0.12). Cosmetic results after surgery were 1.72 in lat and 1.90 in med (p=0.014). These values changed 5 years after radiotherapy with 1.97 and 2.16 respectively (p=0.001). Conclusion: The medial turnout location in the breast is associated with significant lower survival rates and significant unfavourable cosmetic results. The reason may lie in the fact that the pathological stage of the internal mammary chain is unknown, while in lateral tumours all patients with positive axillary nodes underwent systemic therapy and (in part) supraclavicular irradiation. Surgery in the medial part of the breast results in a poorer costactic outcome compared to lateral tumours. The results of our patient data reported above strongly suggest radiotherapy to the IMC nodes. An ongoing EORTC trial will give more information on this topic in a few years.
Wednesday/Thursday, 18-19 September 2002 S 135
established for patients with different TGF-~I genotypes. Results: The TGF-~I codon 25 Arg/Arg genotype was identified in 33 patients and Arg/Pro was identified in 8 patients. Dose-response curves for these two groups differed from each other with an enhancement ratio of 1,10 (95% CI 1,01-1,21) related to the Arg/Pro genotype. No association was observed between TGF-61 codon 25 genotype and acute reactions, nor was any association found between the two other assessed polymerphisms and any type of normal tissue reaction. Conclusion: Our data indicate that the TGF-131 codon 25 Arg/Pro genotype increases risk of radiation-induced subcutaneous fibrosis. However, our data are inconsistentwith previous findings suggesting that the Pro haplotype in codon 25 is associated with tower levels of circulating TGF-6 1 and decreased risk of different fibrotic disorders. This may be a reflection of the complexity and context dependency often being related to cytokine systerns, in order to confirm our result, we intend to apply the analysis to the remaining patents in the historic cohort. This study will be based on DNA isolated from histological archive material (formalin fixed, paraffin embedded sections of non-metastatic axillary lymph nodes or other normal tissue). 406
Poster
Radiotherapy and immediate breast reconstruction using i/e expander following mastectomy for breast cancer A. Richard Taller 1, N. Salem 1, P. Ananian 2, L. Gonzague Casablanca 1, V. Moutardiet 2, B. Lelong2, J. Guiramand2, S. Arnaud 2, R. Zalta2, G. Houvenaeghel2 1paoli Calmettes, Radiotherapy, Marseille, France 2paofi Calmettes, Surgery, Marseille, France Purpose: To assess the toxicity of radiotherapy associated with immediate breast reconstruction (IBR) using tissue expander and implant. Cosmetic results were also evaluated as second criteria, Methods and materials: From January 1999 to December 2000, all patients undergoing IBR using an expander/implant were retrospectively evaluated with respect to complications, rate of reconstruction failure, time for adjuvant treatment and aesthetic results. The majority of patients received also radiotherapy, most of them after reconstruction. Evaluation of complications was obtained by review of the patient chart, and aesthetic results were assessed with subjective self-assessment of patient satisfaction, Results: Seventy eight patients underwent mastectomy and IBR using an expander/implant. Fifty six (72%) received also radiotherapy either before or after reconstruction. The median dose delivered to the reconstructed breast (or the chest wall) was 50 Gy (45-60 Gy), including boost, in 2 Gy fractions. The median follow-up was twenty months (range 14-25 months), Complications were observed in 39.7 percent of cases and appeared correlated with radiotherapy (14% for non irradiated patients; 52% for irradiated patients; p=0.0001). Breast reconstruction failure was observed in 22 percent of cases and was not significantly dependant with irradiation (27% for irradiated patients vs 9% without irradiation; p=0.12). Tamoxifene (TMX) was not correlated with complications (43% with TMX vs 34% without; p=0.47), nor for breast reconstruction failure (19% with TMX and 24% without, p=0.6). Chemotherapy was correlated with higher complications and with significantly higher breast reconstruction failure (51% vs 27% (p=0.029) and. 34% vs 8% (p=0.012), respectively). Chemotherapy was never delayed. Self-assessment of patient satisfaction is ongoing, Conclusion : Immediate breast reconstruction using an expander/implant is safe and can be offered even when adjuvant treatment is required. Surgoons should be aware that complications and reconstruction failure rate are more frequent for patient undergoing post-implant radiotherapy. 407
Poster
Postmastectomy radiotherapy in 1-3 positive nodes J. Sa/inas 1, A. Pi~ero2, R. Garcia F3, M. De/as Heras 1 1Hospital Virgen de/a Arrixaca, Dept. of Radiotherapy, Murcia, Spain 2Hospita/Virgen de/a Arrixaca, Dept. of Surgery, Murcia, Spain 3Hospita/ Virgen de/a Arrixaca, Data Manager, Murcia, Spain Postmastectomy radiotherapy in breast carcinoma with 1-3 positives nodes remain a controversial issue. The impact on survival depend on reduce Ioco-regional relapse. Relapse rate in this population vary from 5 to 30% in majority of series, We analyze in our institution Ioco-regional relapse as first event in patients with breast carcinoma and the next criteria: completely excised by radical mastectomy and axilary dissection, free margins, pT1 or pT2 and one to three metastatic nodes. Between 1980 and 1969, 90 patients fulfilled the above criteria.
Characteristics of the patients and tumors were as follow (%): Age: mean 51 (23-88). Menopausal status: pro 47; post 53. Maximum diameter: mean: 2,87 cm (0.9-5). T-stage: T1 31,5; T2 68,5. Histology: ducta197. Histological differentiation: well 5; moderate 60; poorly 35. Necrosis 17. Vascular invasion 10. Number of isolated nodes: mean 10 (3-24). Number of affected nodes 1 : 41; 2: 30; 3: 29. Extracapsular extension 11. Adjuvant treatment: radiotherapy 7, chemotherapy 40 and hormonal therapy 26. Minimal follow-up were 10 years for patients alive. Results: Loco-regional relapse: 20/90: 22% (75% during the first three years) 10-yr Ioco-regional relapse free survival: 78,5 + 5% Univariant analysis (Cross-Tab: Chi-square, mantel-haenszel and fisher exact text; Kaplan-Meier: log-rank and breslow): age under 35 (37,5 vs. 21), premenopausal status (28,5 vs 16,5), poorly differentiated tumor (33 vs 21,5); T2 stage (29,5 vs 7); tumoral necrosis (50 vs 25) and vascular invasion (50 vs 27) showed higher rate of Ioco-regional relapse but only T-stage was statistically significative (p= 0.0201). Conclusion: The rate of Ioco-regional relapse in patients with 1-3 positve nodes is enough to preclude postoperative radiotherapy in spite of sistemic therapy. The low toxicity of modern radiotherapy appears to justify its use in all but individualized case iT1 stage, low grade, postmenopausal). The impact on survival will come from results of multinational randomized studies presently ongoing. 408
Poster
The radiotherapeutic management of breast cancer: a comparison between different european countries A. Taclhian, E. Ceilley, S. Goldberg, L. Grignon, L. Kachnic, S. Powell Massachusetts General Hospital, Radiation Oncology, Boston, U.S.A. Purpose: Compare the radiotherapeutic management of breast cancer in the different European countries. Methods: An international survey was sent to ESTRO members regarding their individual management of breast cancer. The results of 422 respondents from Europe are presented. For statistical analysis, the responses were grouped by countries as follows: France/Belgian (Fr.Bel)80 respondents, Germany/Austria/Switzerland (Ger.Au.Sw) 93, Italy 45, Spain/Portugal (Sp.Por) 50, Netherlands/Finland/Sweden/Denmark "North" 78, England/Scotland/Ireland (Eng.Sc.lr) 24 and Eastern Europe "East" 44 respondents. Results: Tumor Margins: Physicians were diverse in their definition of negative margins after lumpectomy for invasive cancers. Overall, 28% considered no tumor cells seen at the inked margins to be negative. This varied between 8% for Eng.Sc.lr and 46% for the North countries (p<0.001). 29% considered no tumor cells seen at <5 mm (range 38% for Eng.Sc.lr and 25% for East p<0.001). Post-mastectomy RT: There were significant differences in management techniques for patients after mastectomy. Overall, 84% of Europeans use post-mastectomy radiation (PMRT) in T3N0 lesions. This varied between 60% in Italy and 96% in Sp.Por. Only 67% in North used PMRT (p<0.01). In the 1-3 lymph node positive (LN+), 60% of European chose PMRT (range 19% in Italy and 74% in Sp.Por). In North countries 36% chose PMRT (p<0.001). In the >4LN+, 93% use PMRT varying between 88% and 97% with the exception of Italy where only 65% selected PMRT (p<0.01). 21% of respondents chose to treat the supraclavicular area (5% in Italy to 29% in Sp.Por, p<0.001) in T3N0, 41% (3% in Italy to 73% in Fr.Bel p<0.001) in 13 LN+ and 93% (63% in Eng.Sc.ir to 100% in North p<0.05) in >4 LN+. Regarding the axiila, 9.2% chose to use PMRT (0% in Italy and Eng.Sc.lr to 18% in East, p<0.0001) in T3N0, 14% (0% in Italy to 33% in East p<0.001) in 1-3 LN+ and in 53% (29% in Eng.Sc.lr to 81% in North p<0.05) in >4LN+. 10% chose to treat IMC (0% in Italy to 19% in Fr.Bei, p<0.001) in T3N0, 23% (0% in Italy to 49% in Fr.Bel p<0.01) in 1-3 LN positive, 35% (15% in Italy to 57% in FR.Bel p<0.01) in >4 LN+. Differences in regional RT after lumpectomy and DCIS will be presented. Conclusions: There are differences in the management of breast cancer between European countries. International surveys could lead to the design of prospective studies to define the optimal use of RT in the treatment of breast cancer. 409
Poster
A dosimetric and treatment planning comparison between brachytherapy and single field electrons for breast boost irradiation P. Ocamoo. P. Thirion, P. McCavana, A. Downes, S. Gdm/ey, J. Armstrong, C. Ke//y St. Luke's Hospita/, Physics, Dublin, ~re~and Introduction: Clear evidence for breast boost therapy is shown in a ran-
S 136 Wednesday/Thursday, 18-19 September 2002
domised EORTC trial (2288/10882) on patients who have undergone tumourectomy and whole breast irradiation. Choosing the optimum modality for the boost is a topical issue, and one of concern in the radiotherapy community, By using full 3D CT planning, this study compares the dosimetry and treatment planning characteristics of both HDR interstitial brachytherapy and electron beam radiotherapy for the delivery of a breast boost. Materials and Methods: This study is set out to accumulate 10 patients for technique comparison. Selection criteria were based on previous lumpectomy, whole breast EBRT and referral for HDR optimised brachytherapy. The subjects were CT scanned post implantation and images sent to PLATO BPS (brachytherapy planning system) and HELAX TMS (electron beam planning system). A matched Planning Target Volume (PTV) was then drawn. Dose Volume Histograms (DVH) were obtained for target volume, Organs at Risk (OAR) and implant. From this data, an assessment of the surface dose, PTV coverage, homogeneity of dose distribution and irradiation of organs at risk were then obtained, Results: Initial results indicate that a more homogenous dose distribution and higher coverage are obtained with electrons, if optimal selection of energy and applicator is carried out and that treatment is designed with the aid of CT planning. Brachytherapy on the other hand, provides a lower surface dose and a smaller treated volume of breast tissue. Dose to the OAR is within acceptable limits with both modalities but with is again indicated lower with_ electron treatments, Conclusions: Treatment planning analysis indicates significant differences between modalities. From the dosimetric point of view, electrons are indicared in cases where dose to the OAR's and good homogeneity are of more clinical import than dose to the surrounding breast tissue and cosmesis, 410 Poster T a r g e t e d intraoperative radiotherapy for breast cancer (Tar-
git): an international trial
J.S. Vaidya 1, D. Joseph2, B.S. Hilaris 3, J.S. Tobias 1, ,I. Houghton 1, M. Keshtgar 1, R. Sainsbury 1, L Taylor 1, M. Baum 1 1University College London, Surgery, London, UK 2Sir Charles Gairdner Hospital, Radiation Oncology, Nedlands, Australia 3New York Medical College, Radiation Oncology, New York, USA
Posters
411 Poster I n c r e a s e o f collagen
synthesis correlates with radiationinduced skin edema in breast cancer patients
Ft. Keskikuru 1, J. Nuutinen 1, A. Jukkola 2, V. Kataja 1, J. Risteli 3, T. Lahfi~1
1Kuopio University Hospital, Department of Oncology, Kuopio, Finland 20ulu University Hospital, Department of Oncology, Oulu, Finland 3University of Oulu, Department of.Medical Biochemistry, Oulu, Finland Purpose: Tissue hypoxia is related to the formation of tissue edema. Tissue hypoxia in the skin can be assessed by measuring the temporal variation of skin thickness after radiotherapy (RT). Variations of skin thickness were correlated with the marker of skin collagen synthesis in order to investigate their possible interrelationship. Material and Methods: Skin suction blisters were induced in irradiated and non-irradiated skin during RT and during follow-up (up to 2 years) in 21 breast cancer patients treated with breast conserving surgery and converttionally fractionated RT to 50 Gy. From skin suction,~blister fluid the procollagen concentration of type I collagen (PINP) was determined by a spesific radioimmunoassay. Concomitantly, the skin thickness was measured with a high frequency ultrasound (20 MHz). Results: Collagen synthesis starts to increase during RT while the skin thickness of the irradiated skin remains unchanged. The maximum level of the type I collagen synthesis was observed at 4 and 7 months postirradiation when also the skin thickness was markedly elevated. The correlation was statistically highly significant (p<0.005). After 7 months both the thickness of the irradiated skin and skin collagen synthesis declined to their protreatment levels during the follow-up period. Conclusion: We demonstrated significant changes both in skin thickness and collagen metabolism following conventionally fractionated RT in breast cancer patients. The results suggestthatthickeningof theskin is duetothe formation of skin edema and thus skin hypoxia which further stimulates collagen synthesis. 412 Poster T h e m e d i a l turnout location - An unfavourable prognostic fac-
tor (review of 1089 patients, 1984 - 1995) Breast conserving surgery followed by whole breast radiotherapy (including a tumour bed boost) is the current gold standard for operable breast cancer. However, symptomatic local recurrence occurs usually at the site of primary tumour, suggesting that it may be unnecessary to irradiate the whole breast. Also, it is estimated that up to 50% of local recurrence is attributable to 'geographical miss' by the boost dose. We have pioneered* the use of intra-operative radiotherapy delivered to the tumour bed under direct vision in a routine operation theatre using a novel portable radiotherapy device (Intrabeam, Pec) that delivers soft x-rays at 50Kv from the surface of a spherical applicator, which is available in various sizes and is inserted into the tumour bed after wide local excision of the turnout. The physical dose is 20Gy at the surface of the applicator and 5Gy at lcm depth. The estimated biologically effective dose at the surface is 50-120Gy, with a high therapeutic ratio between tumour bed and skin or lung dose. Cardiac protection is easily provided with a thin tungsten impregnated sheet on the posterior tumour bed, if on the left side. The pilot study in the UK using this technique (n=25) as a substitute for the boost was encouraging* - at a median follow up of 34 months no recurrences were reported and cosmetic appearance was good. The US (39) and the Australian (15) centres have treated 84 patients in local feasibility studies. We are embarking upon a multicentre randomised trial to test whether such an approach could replace the 6-wks of postoperative radiotherapy for infiltrating duct carcinoma. The UK centre has randomised 29 patients. Thus a total of 94 patients has been treated with the novel technique. The longest follow up is 45 months (median=18m). Our 3rd patient had skin necrosis due to the applicator surface being brought too close to it. The technique was modified and there has been no further toxicity. In the randomised UK patients there was one local recurrence at 22 months. This was a protocol violation; she had involved margins but did not have re-excision. Several centres in the USA, UK, Europe, India and Australasia are keen to participate in this trial. If proven, this approach could potentially save time, money and breasts both for hospitals and their patients. *Targeted intra-operative radiotherapy (Targit):An innovative method of treatment for early breast cancer JS VaJdya M Baum JS Tobias et al Ann Oncol 2001;12:1075-80
J. Hammer, C. Track, D.H. Seewa/d, K. Spieg/, ,1. Feichtinger Barmherzige Schwestern Hospital, Dept. of Radiotherapy, Linz, Austria Purpose: The authors report on the unfavourable results in survival and comesis in patients with medially located breast tumours (reed) compared to patients with cancer in the lateral quadrants (lat). Patients and Methods: From 1984 to 1995, 1089 patients with 1100 T1-2 N0-1 tumours were treated. 707 presented with lat, 294 with reed, and in 99 cases the primary tumour was located in the central region of the breast (centr). The prospective treatment method included breast conserving surgery and radiotherapy with 45 to 50 Gy to the whole breast. The internal mammary lymph node chain (IMC) was not electively irradiated. In 1025 patients a boost has been performed: 650 patients underwent an interstitial 10 Gy boost in 1 fraction, 375 an external beam boost (electrons or photons) and 75 had no boost. All axillary nodal positive patients underwent systemic therapy (6 x CMF or Tamoxifen). Mean follow up of survivors: 97 months (36 to 192 months). Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test. From 518 patients the cosmetic results were evaluated using a 4 grade scoring system. Results: Comparin~Tffed-and lat the actuarial survival parameters are highly significant in favour of the lateral turnouts (p-values: overall survival 0.025, disease specific survival 0.025, disease free rate 0.011). No significance is given in local oontrol (p = 0.12). Cosmetic results after surgery were 1.72 in lat and 1.90 in med (p=0.014). These values changed 5 years after radiotherapy with 1.97 and 2.16 respectively (p=0.001). Conclusion: The medial turnout location in the breast is associated with significant lower survival rates and significant unfavourable cosmetic results. The reason may lie in the fact that the pathological stage of the internal mammary chain is unknown, while in lateral tumours all patients with positive axillary nodes underwent systemic therapy and (in part) supraclavicular irradiation. Surgery in the medial part of the breast results in a poorer costactic outcome compared to lateral tumours. The results of our patient data reported above strongly suggest radiotherapy to the IMC nodes. An ongoing EORTC trial will give more information on this topic in a few years.