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752 poster DOSIMETRIC BENEFIT OF POSTERIOR AXILLARY BOOST ON THE AXILLARY LYMPH NODES IN BREAST CANCER J. H. Lee1 , M. J. Chung1 , J. Y. Kim1 , G. W. Lee1 , W. C. Park2 , S. M. Chung1 1 C OLLEGE OF M EDICINE , T HE C ATHOLIC U NIVERSITY OF KOREA, Department of Radiation Oncology, Seoul, Korea Republic of 2 C OLLEGE OF M EDICINE , T HE C ATHOLIC U NIVERSITY OF KOREA, Department of General Surgery, Seoul, Korea Republic of Purpose: Posterior axillary boost(PAB) technique has been widely used for years, but this technique is still unclear about the effect in the optimal dose coverage. The purpose of this study was to evaluate the lymph node coverage of a computed tomography(CT)-based posterior axillary boost technique in the advanced breast cancer patients. Materials: CT simulation data of 20 consecutive patients who were treated with breast conserving surgery and axillary lymph node(ALN) dissection followed by radiation therapy including supraclavicular(SCV) field were selected. Level II and III ALNs, ipsilateral lung and brachial plexus were anatomically delineated. Plans using three techniques were generated. Three techniques were (1) anterior oblique supraclavicular field alone (AP); (2) anterior oblique supraclavicular field using wedge (APW); and (3) anterior oblique supraclavicular field using posterior axillary boost(AP-PAB). Standard rules for the plans were; (1) level II and III ALN volume percentage that receiving more than 95% of prescribed dose was 90% or more, (2) brachial plexus should not received more than 107% of prescribed dose, and (3) PAB field was designed to supplement to any insufficient region of the ALNs delineated on CT images. Fifty Gy was prescribed to the ALNs. Results: Mean treatment volume percentage receiving more than 90%(V90) and 95%(V95) of prescribed dose were 99.5% and 95.5% in AP-PAB, compared to 85.8% and 63.0% in AP (p<0.001), and 97.6% and 88.0% for APW, respectively(p=0.023 and p=0.001, respectively). AP-PAB showed higher mean treatment volume percentage receiving more than 107%(V107) of prescribed dose than AP(17.9% vs. 5.7%; p<0.001), but similar with APW (14.8%; p=0.344). Homogeneity index(HI) in AP-PAB was also superior to the other plans(p<0.001). Mean dose of ipsilateral lung increased in AP-PAB compared to APW(46.2% vs. 46.0%; p=0.041), but ipsilateral lung volume receiving more than 20 Gy did not(23.9% vs. 23.8%; p=0.105). Mean irradiated volume receiving more than 40 Gy in AP-PAB was significantly less than that in APW(573.3 cc vs. 607.8 cc, respectively; p<0.001). In terms of AP-PAB, V95 and HI increased more significantly in patients with deep ALN(maximum depth≥7cm) than those with shallow ALN(maximum depth<7cm)(p=0.011 and p<0.001, respectively). On the other hands, brachial plexus dose and irradiated volume decreased more in deep ALN group than in shallow ALN group(p=0.022 and p=0.028).
Purpose: We report the early toxicity of our forward planned IMRT(FIMRT) approach, in low risk breast cancer patients treated with Hypofractionated Whole Breast Irradiation(HWBI). Materials: From 02/2009-06/2010 221 patients were treated with HWBI with a schedule similar to the one of the START B trial, i.e. whole breast, 40 Gy/ 15 fractions, delivered in 3 weeks. The patient median age was 61 years (28-84 yrs). The FIMRT approach was chosen to reduce skin toxicity that can be registered with hypofractionation, maintaining a short time of treatment planning and patient delivery.A median number of 4 segments were used(28) within a tangential two field irradiation technique. 65,8% of the patients needed 4 segments to obtain an homogeneous dose, with hot spots ≤ 108% on PTV, and with 3% of the heart≤ 40 Gy D2Eq, and ≤15% of ipsilateral lung≤ 25 Gy D2Eq. For 29,7% of patients the classic 2 fields have been enough to reach the dose costraints. The rest of the patients ( 3,5%) needed a combination of 2-4 segments with different energies (6 MV and 18 MV). Skin protection creams were prescribed for all patients. Results: With a median follow-up of 7 months (1-14 months) the patients presented the following RTOG/EORTC acute skin toxicity: 86/221(38,9%) G0, 113/221(51,1%) G1, 20/221(9,1%) G2 and only 2/221(0,9%) G3. None of the patients had to discontinue the treatment. Eleven of the patients presented a delayed (for 8-14 days after the end of RT) maximum toxicity.Considering the quadrants the toxicity was as follows: medial 212(95,9%) ≤G1 vs 9(4,1%) G2; lateral 213(96,4%) ≤G1 vs 8(3,6%) G2; inframmamary fold 204(92,3%) ≤G1vs 15(6,8%) G2 vs 2(0,9%) G3; mammary areola 210 (95%) ≤G1 vs 11(5%) G2; axillary 210(95%) ≤G1 vs 11(5%) G2. Many patients experienced toxicity of only one or two of the quadrants; the most frequent in the inframammary fold, were the 2 cases of G3 toxicity were registered.The effect of chemotherapy on skin toxicity: 59/221 patients had a previous or concomitant chemotherapy (51 of them with anthracyclines) and the skin toxicity was as follow: 20/59(33,9%) G0, 32/59(54,2%) G1, 6/59(10, 2 %) G2 and 1/59(1,7%) G3. 110 patients performed the six months evaluation: 96 of them had no toxicity (87,3%) and 14(12,7%) presented a G1 toxicity, intended as a skin discoloration or a slight hardening of the skin.No other toxicities(to lung or heart) were registered. Conclusions: Large studies that explored the HWBI, some of them with long follow up (> 12 years), have found that fewer, larger doses are as effective as conventional schedules in reducing the risk of recurrence. The FIMRT that we adopted allowed us to get a good result of acute and subacute skin toxicity, proving that a shorter, cheaper and more convenient three-week course of radiation can be adopted for most patients with early stage breast cancer. 754 poster ELECTROMAGNETIC PROPERTIES OF BREAST CANCER I. Marinova1 , A. Chakarova2 , V. Mateev1 T ECHNICAL U NIVERSITY OF S OFIA, Department of Electrical Apparatus, Sofia, Bulgaria 2 N ATIONAL H OSPITAL OF O NCOLOGY, Department of Radiotherapy, Sofia, Bulgaria
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Conclusions: Addition of PAB to the anterior oblique SCV field improved dosimetric coverage of ALNs without increase of lung or brachial plexus dose. This effect of PAB increased in deep ALN patients. 753 poster EARLY TOXICITY RESULTS OF A FORWARD PLANNED HYPOFRACTIONATED IMRT FOR WHOLE BREAST ADJUVANT TREATMENT A. Fodor1 , A. Bolognesi1 , P. Mangili2 , M. Pasetti1 , C. Fiorino2 , A. Chiara1 , I. Dell’Oca1 , S. Broggi2 , A. Deli1 , N. Slim1 , G. Cattaneo2 , E. Villa1 , B. Pappalardi1 , R. Calandrino2 , N. G. Di Muzio1 1 S AN R AFFAELE S CIENTIFIC I NSTITUTE, Department of Radiotherapy, Milan, Italy 2 S AN R AFFAELE S CIENTIFIC I NSTITUTE, Medical Physics, Milan, Italy
Purpose: Determination of exact electromagnetic properties of human tissues as electric permittivity - , magnetic permeability - μ and electric conductivity σ are of paramount importance for investigations of electromagnetic fields distributions in human body. The difference between normal and cancer tissues properties values can be used for effective electromagnetic diagnostic and treatment methods and procedures such as impedance tomography, radio frequency ablation, etc. Materials: Computerized measurement system for electromagnetic field property determination based on electric bioimpedance measurements is set up. The measurement system is composed of precision impedance analyzer Agilent 4294A, tissue test fixture and computer system. The measurement frequency range is from 40Hz to 110MHz. The system is applied for measurements of surgically extracted pairs of tissue samples which contains a normal and cancer material both acquired from a same patient. Results: Electrical conductivity σ and electrical permittivity due to current flow or polarization induced by an electric field in matter under investigation are measured. These properties are determined by measurement of bioimpedance using known shape and sizes of samples. The developed approach is addressed to characterizing of the electromagnetic properties of breast cancer in all stages. Electric impedance amplitude and angle of breast tissue samples are shown in Fig.1, here the normal tissue is with better conductivity in whole frequency range. Impedance frequency spectrograms are not the same for different persons, but values of tumor and normal tissues are always different for one patient.
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were postmenopausal. Modified radical mastectomy and breast conserving surgery rate were 55.2% and 29.3%, respectively. Adjuvant radiotherapy and adjuvant chemotherapy were prescribed in 51 (87.8%) and 56 (96.6%) patients, respectively. BRCA 1 mutation on exon 2 and 20 were positive in two and two patients respectively and there was no statistically significance with Her-2 status (p=0.528). BRCA 2 mutation was positive in 7 patients and all of them were Her-2 negative but it was not statistically significant (p=0.067). There was no association with BRCA 1-2 gene mutation with stage, lymph node involvement, histological and nuclear grade, lymphovasculary and perineural invasion (p>0.05).
Conclusions: Electric impedance measurements were performed on breast cancer human tissue samples at different frequencies. The electromagnetic properties of human tissues are determined by electric impedance data. Tumor and normal tissues can be distinguished on their impedance frequency spectrums. Acknowledgement: This work was supported by the National Science Fund of the Ministry of Education and Science of Bulgaria under Contract "D002-157/2008". 755 poster ENHANCED RAD21 COHESIN EXPRESSION CONFERS POOR PROGNOSIS AND RESISTANCE TO CHEMOTHERAPY IN HIGH GRADE LUMINAL, BASAL AND HER2 BREAST CANCERS M. McKay1 , H. Xu2 , M. Yan3 , Y. Yan2 , R. Ramsay2 , R. Sutherland4 , S. Fox3 1
T HE C ANBERRA H OSPITAL AND AUSTRALIAN N ATIONAL U NIVERSITY, Radiation Oncology Department, Canberra, Australia 2 P ETER M AC C ALLUM C ANCER C ENTRE, Department of Research, Melbourne, Australia 3 P ETER M AC C ALLUM C ANCER C ENTRE, Department of Pathology, Melbourne, Australia 4 G ARVAN I NSTITUTE FOR M EDICAL R ESEARCH, Sydney, Australia Purpose: RAD21 is a component of the cohesin complex, which is essential for chromosome segregation and error-free DNA repair. We assessed its prognostic and predictive power in a cohort of in situ and invasive breast cancers, and its effect on chemosensitivity in vitro. Materials: RAD21 immunohistochemistry was performed on 345 invasive and 60 pure in-situ carcinomas. Integrated genomic and transcriptomic analyses were performed on a further 48 grade 3 invasive, cancers. Chemosensitivity was assessed in breast cancer cell lines with an engineered spectrum of Rad21 expression. Results: RAD21 expression correlated with early relapse in all patients (HR 1.74, 95% CI 1.062.86, p=0.029). This was due to the effect of grade 3 tumors (but not grade 1 or 2) in which RAD21 expression correlated with early relapse in luminal (p=0.040), basal (p=0.018) and HER2 (p=0.039) groups. In patients treated with chemotherapy, RAD21 expression associated with shorter overall survival (p=0.020). RAD21 mRNA expression correlated with DNA copy number, with amplification present in 32% (7/22) of luminal, 31% (4/13) of basal and 22% (2/9) of HER2 grade 3 cancers. Variations in RAD21 mRNA expression in the clinical samples were reflected in the gene expression data from 36 breast cancer cell lines. Knockdown of RAD21 in the MDAMB-231 breast cancer cell line significantly enhanced sensitivity to cyclophosphamide, 5-fluorouracil and etoposide. The findings for the former two drugs recapitulated the clinical findings. Conclusions: RAD21 expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers. RAD21 may be a novel therapeutic target. 756 poster
EVALUATION OF BRCA 1-2 GENE MUTATIONS IN PATIENTS WITH TRIPLE NEGATIVE AND ER(-), PR(-), HER-2(+) BREAST CANCER M. C. Uzal1 , S. Sener2 , A. Özen1 , S. Cakina2 , T. Sipahi2 , R. Cosar1 , T. Gulyasar2 , H. Karagol3 , O. Yalcin4 1 T RAKYA U NIVERSITY M EDICAL FACULTY, Radiation Oncology, Edirne, Turkey 2 T RAKYA U NIVERSITY M EDICAL FACULTY, Biophysics, Edirne, Turkey 3 T RAKYA U NIVERSITY M EDICAL FACULTY, Medical Oncology, Edirne, Turkey 4 T RAKYA U NIVERSITY M EDICAL FACULTY, Pathology, Edirne, Turkey Purpose: We aimed to evaluate BRCA 1-2 gene mutation in breast cancer patients with worst prognostic factors such as triple negative and ER negative, PR negative, Her-2 positive. Materials: We studied 58 women who were treated with triple-negative and ER negative, PR negative, Her-2 positive breast cancer. Patients data reviewed retrospectively. All blood samples were analyzed with PCR-SSCP for BRCA 1 (185delAG exon2 and 5382insC exon20) - 2 (6174delT) gene mutation. Results: Patients characteristics are shown in Table 1. Median age was 53 (31-75). 30 (51.7%) patients were premenopausal and 28 (48.3%) patients
Conclusions: We could not find any association between BRCA 1-2 gene mutation with different histopathological findings in breast cancer patients with worst prognostic factors such as triple negative and ER negative, PR negative, Her-2 positive. 757 poster EVALUATION OF SICAM-1 AS A MARKER OF LUNG INJURY IN BREAST CANCER PATIENTS UNDER RADIATION TREATMENT M. Piperi1 , E. Kalogera2 , X. Provatopoulou2 , G. Zografos3 , E. Athanasiou1 , A. Gounaris2 1 AG . A NARGYROI O NCOLOGICAL H OSPITAL, Radiation Oncology, Athens, Greece 2 H ELLENIC A NTICANCER I NSTITUTE, Research Center, Athens, Greece 3 H IPPOKRATIO H OSPITAL, 1st Department of Propaedeutic Surgery, Athens, Greece Purpose: Injury to the alveolar epithelium and the vascular endothelium is a key component of the pathogenesis of acute lung effects. Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be an important mediator of neutrophil recruitment and trafficking into the lung, since increased expression has been demonstrated in the setting of acute lung injury. In an effort to explore the prognostic and pathogenic significance of sICAM-1 in radiationinduced side effects, we investigated its expression in serial blood specimens of breast cancer patients undergoing radiation treatment. Materials: In a prospective single-center study, sICAM-1 plasma levels were measured in 38 breast cancer patients under radiation therapy and 10 healthy controls. The mean age of the patients was 51.97 ± 11.62 years. Peripheral venous bloodsamples were collected prior to, during (9th day), at completion of radiation treatment (38th day) and after a follow up of 2 months (90th day). The determination of plasma sICAM-1 levels was performed in duplicates, using Milliplex Map Immunoassay kits in a Luminex Bioanalyzer (Luminex Corp, Texas, USA). All patients received a total dose of 50 Gy (2 Gy daily for 5 weeks), whereas 29/38 patients received an additional boost. Results: Patients were assigned into 2 groups, according to their median sICAM-1 plasma levels; 31/38 (81.58%) patients were assigned to group A and 7/38 (18.42%) to group B. Group A patients exhibited low expression levels of sICAM-1 throughout the study period (Prior: 132.84 ng/ml, 9th day: 127.53 ng/ml, 38th day: 133.65 ng/ml, 90th day: 128.97 ng/ml). Higher plasma levels of sICAM-1 were observed in patients of group B (Prior: 310.55 ng/ml, 9th day: 242.54 ng/ml, 38th day: 234.87 ng/ml, 90th day: 256.32 ng/ml). It is noteworthy that in group B patients, sICAM-1 expression was elevated both