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can sensitize Breast cancer cells and cancer initiating cells to Radiation. Materials/Methods: Cell culture and treatment: MDA MB-231 and MCF7 human Breast cancer cell lines were cultured. Cells were maintained at 37 C in 5% co2 incubator to 80-90% cell confluence and then used in the assay. Curcumin & Piperine Dilution: Curcumin is an active ingredient extracted from the rhizome of plant Curcuma longa whereas piperine is an active ingredient extracted from the seeds of Piper nigrum. Curcumin 1 mg/ml and piperine 5 mg/ml was dissolved in Dimethyl Sulphoxide DMSO to get stock solution. From this working concentration were dissolved in DMEM media. Cell viability Assay: MTT assay was done to assess the cell viability. Cells were cultured in 96 well plates at a density of 7 x 104 cells/well. After 24 hrs incubation cells were treated with different concentration of Curcumin, Piperine, and an equal concentration of DMSO and drug kinetics were performed for 24, 48 and 72 hrs. After incubation with drug media removed at different time points as indicated and cells were treated with MTT solution at concentration 0.45 mg/ml and incubated for 3 hrs at 37 C. Formazan crystals that were formed solubilized in DMSO and absorbance was measured at 570 nm using micro plate reader. Breast cancer cell lines were treated with various concentrations of Curcumin and Piperine from 10 mM to 2.5 mM. Further combined Curcumin 5 mM and Piperine 10 mM individually with Radiation 2, 4, 6, 8, 10 Gy in 1 fraction in Breast cancer cells. Results: At 10 mM Curcumin, Piperine concentration loss of cell viability is 75% with Curcumin whereas in Piperine no effect is seen. Combination of Curcumin 5 mM and Piperine 10 mM individually with Radiation 2,4, 6, 8, 10 Gy in 1 fraction in Breast cancer cells we found that at 8 Gy 80% reduction in cell viability in Curcumin Radiation, Piperine Radiation compared to Radiation alone with 50% reduction cell viability. Curcumin and Piperine exhibited anticancer effects in Breast cancer cell lines MDAMB-231 and MCF-7. Conclusions: Our preliminary data indicates that Curcumin and Piperine sensitize Breast cancer cells to radiation in dose dependent manner. In addition we will investigate the effect on primary tumor cells and cancer initiating cells of Breast cancer patients. Author Disclosure: N. Thammineni: None. M. Vara Lakshmi: None. K. Nandaki Nag: None. Z. Shahabeh Abbas: None. P. Thammineni: None. B. Kanaka: None. V. Sri Harikrishna: None.
Comparison of Acute Radiation Injury of the Skin and Cosmetic Outcome Between SIB-IMRT and Late-Course Boost-IMRT for Early Breast Cancer After Breast-Conserving Surgery S. Wang,1 H. Xing,2 J. Li,1 Z. Ying Jie,2 M. Xu,1 Y. Ding,2 and W. Wang1; 1 Shandong Cancer Hospital, Jinan, China, 2Shandong Cancer Hospital, Jinan, China Purpose/Objective(s): To explore the difference on acute radiation injury of the skin and cosmetic outcome after breast conserving therapy for early breast cancer between the simultaneous integrated boost intensity modulated radiation therapy (SIB-IMRT) and late-course boost intensity modulated radiation therapy (late-course boost-IMRT). Materials/Methods: For this study, 353 female breast cancer patients (stages I-II), treated with breast-conserving surgery at the institute between November 2002 and February 2012, were retrospectively identified. Median age at diagnosis was 43 (range 20-67) years. Two hundred eighteen patients were treated with SIB-IMRT after breast conserving therapy and 135 patients were treated with late-course boost-IMRT. The tumor bed was delineated and expanded with a margin of 10-15 mm to generate boost planning target volume (PTVt). The whole breast was expanded with a margin of 5 mm to generate the breast PTVb. For the SIB-IMRT group, fractionation schemes used were 27-28 daily fractions of 1.8-1.9 Gray (Gy) to the PTVb and 2.15-2.3 Gy to the boost PTVt. For the late-course boostIMRT group, fractionation schemes used were 25 daily fractions of 2.0 Gy to the whole breast PTVb, then 5-8 daily fractions of 2.0 Gy to the boost PTVt only. We estimated difference of the two groups on acute radiation injury of the skin and cosmetic outcome according to RTOG and Harris’ cosmetic criterion based on the Log-Rank and c2 test. Results: Median follow-up was 62 (range 1-144) months. The two groups had comparability on age, stages, histopathology, hormone receptor status, postoperative chemotherapy (all P value > 0.05). For all patients, OS was 98.71%, 96.68%, 94.51% at 3, 5, 10-years, respectively. DFS was 95.34%, 90.55%, 88.15% and LCR was 96.86%, 95.43%, 94.60% at 3, 5, 10-years for the whole group, respectively. The 3, 5, 10-year LRR were 3.13%, 4.57%, 5.4% and the DMR was 0.60%, 2.54%, 2.94% for the patients, respectively. There was no significant differences between the SIB-IMRT and late-course boost-IMRT group (X2 Z 0.01, P Z 0.91). For the acute radiation injury of the skin, there were 155, 56, 7 cases and 86, 43, 5 cases at 1, 2, 3 degree for the SIB-IMRT and late-course boost-IMRT group, respectively. There was no significant differences between the SIB-IMRT and late-course boost-IMRT group (X2 Z 1.85, P Z 0.40). Meanwhile, in cosmetic outcome, there were 187, 22, 8, 1 cases and 109, 17, 7, 1 cases at great, good, general, bad for the SIB-IMRT and late-course boost-IMRT groups, respectively. There was no significant differences between the SIBIMRT and late-course boost-IMRT group (X2 Z 1.29, P Z 0.30). Conclusions: In conclusion, SIB-IMRT had the same survival comparing with late-course boost-IMRT. Meanwhile, the acute radiation injury of the skin and cosmetic outcome was the same as late-course boost-IMRT. Therefore, it was worth to popularize in clinical. Author Disclosure: S. Wang: None. H. Xing: None. J. Li: None. Z. Ying Jie: None. M. Xu: None. Y. Ding: None. W. Wang: None.
2073 Studying Whether Curcumin and Piperine Sensitize Breast Cancer Cells and Breast CancereInitiating Cells to Radiation N. Thammineni, M. Vara Lakshmi, K. Nandaki Nag, Z. Shahabeh Abbas, P. Thammineni, B. Kanaka, and V. Sri Harikrishna; KIMS, Secunderabad AP, India Purpose/Objective(s): Breast cancer is a major cause of morbidity and mortality in economically developing countries such as India. In spite of advances in diagnosis and therapy mortality rate is higher in Breast cancer patients due to resistant to current treatments. Recent preclinical studies have shown that Curcumin and Piperine agents as potent radio sensitizers of tumor cells human Cervical, Prostate, and Rhabdomyosarcoma. However it was not known whether Curcumin and Piperine
2074 IMRT Versus 3D-CRT for Postmastectomy Irradiation of Chest Wall and Regional Nodes: A Population-Based Comparison of Normal Lung Dose W. Li,1,2 J. Ma,1,2 J. Chen,1,2 and Z. Zhang1,2; 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Purpose/Objective(s): The role of irradiation of chest wall and regional nodes is widely recognized in the management of breast cancer patients with positive axillary lymph nodes after MRM. Conventional post-mastectomy radiation therapy (PMRT) is often delivered with traditional field borders. Chest wall and regional nodes delineation techniques have been discussed with available contouring guidelines and dosimetric analyses have shown that IMRT could improve the coverage of regional nodes. However, it’s unclear yet whether CT-based inverse IMRT planning to treat chest wall and nodal regions as a whole PTV is superior to conventional technique in terms of normal tissues sparing and injury. We herein conduct a population-based dosimetric study comparing the dose-volume of ipsilateral lung in patients undergoing PMRT using a Linac IMRT technique versus conventional technique. Materials/Methods: During the Period of June 2012 to Dec 2013, 169 breast patients who completed PMRT at our institution were included for analysis. All patients received a total dose of 50 Gy in 25 fractions to the chest wall and supra/infraclavicular region. The inverse-planned IMRT technique treating the chest wall and supra/infraclavicular region as an integrated volume was applied in 78 patients (IMRT group), and
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the conventional technique, including tangential chest wall beams optimized with field-in-field technique, and separate anterior mixed photon-electron beams for supra/infraclavicular region, was used in 91 patients(3D-CRT group). The percent volumes of ipsilateral lung receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), and 30 Gy (V30) extracted from dose-volume histograms (DVHs) were collected and compared between treatment groups. Results: The V5 of ipsilateral lung was lower in the 3D-CRT group (52%7%) than in the IMRT group (65%9%), and their difference was statistically significant (p Z 0.001). The V10 was similar for both groups (41%7% vs 44%4%, p Z 0.052). However, the V20 was higher in the 3D-CRT group (32%6%) than in the IMRT group (29%2%), and there was a statistical significance (p < 0.001). Similarly, the V30 was higher in the 3D-CRT group (22%5%) than in the IMRT group (21%2%), and the difference reached significance as well (p < 0.001). Conclusions: This population-based dosimetric analysis demonstrated that IMRT technique could reduce the V20 and V30, but increase the volume of low dose irradiation of ipsilateral lung (V5), as compared to 3D-CRT technique. Further study is warranted to test whether these dosimetric differences could lead to a difference in the injury of ipsilateral lung. Author Disclosure: W. Li: None. J. Ma: None. J. Chen: None. Z. Zhang: None.
receiving anti-HER 2 treatment before BM (51 m) compared with those did not (27 m), with marginal statistical significance (p Z 0.06). Conclusions: Both anti-HER 2 treatment and chemotherapy after WBRT prolonged OS in HER 2 + breast cancer pts with BM. The greatest survival benefit from anti-HER 2 treatment was observed in pts who had anti-HER 2 treatment only after WBRT. Prior anti-HER 2 therapy in the adjuvant or metastatic setting seemed to prolong the interval from diagnosis of BC to the development of BM. Author Disclosure: J. Chen: None. Q. Zhang: None. X. Yu: None. Z. Zhang: None. X. Guo: None.
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Purpose/Objective(s): To evaluate the supraclavicular nodal failure (SCF) of breast cancer patients with one to three positive axillary nodes treated with breast conserving surgery without supraclavicular nodal radiation and identify risk factors for SCF. Materials/Methods: Two hundred thirty-six breast cancer patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without neoadjuvant systemic therapy from Jan. 2005 to Aug. 2013 were analyzed. All patients received whole breast radiation to a total dose of 46-50 Gy (median 50 Gy) at 2 Gy/f or 43.5 Gy at 2.9 Gy/f. In 233(98.7%) patients, tumor bed was boosted to 58-70 Gy (median 60 Gy) at 2 Gy/f or 52.2 Gy at 2.9 Gy/f. Two patients (0.8%) received supraclavicular nodal radiation and none received axillary or internal mammary nodal radiation. 233 (94.5%) patients received adjuvant chemotherapy, 189 (80.1%) received hormonal therapy and 18 (7.6%) received herceptin. SCF, locoregional recurrence (LRR), distant metastases (DM), and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Results: The median age was 44 years (range, 21-71 years) and the median number of axillary nodes dissected was 19 (range, 6-41).163 patients have T1 disease and 63 T2 disease. With a median follow-up of 43 months (range, 5-108 months), the 5-year SCF, LRR, DM, and OS rates were 4.0%, 4.0%, 5%, 98.6% respectively. Among 8 patients who developed SCR, 4 concurrent with DM and 1 after DM. Age, number of positive axillary nodes and molecular subtype were risk factors for SCF. The 5-year SCF rates were 10.8% and 1.5% for patients < 40 and 40 years old (p Z 0.016), 10.4% and 2.6% for those with 2-3 and 1 positive axillary nodes (p Z 0.004), and 7.2% and 2.9% for those with non-luminal A and luminal A subtype. The 5-year SCF rate was 0%, 4.2%, 15.9%, and 28.6% for patients with 0, 1, 2, and 3 above risk factors. Tumor size, lymph vascular invasion, histology grade, total number of axillary node dissected, ratio of positive axillary node, chemotherapy, hormonal therapy were not associated with SCF. Conclusions: The supraclavicular nodal recurrence is very low for breast cancer patients with one to three positive axillary nodes treated with breast conserving surgery without supraclavicular nodal radiation. Younger than 40 years old, 2 to 3 positive axillary node and non-luminal A subtype are risk factors for SCF. Supraclavicular nodal radiation is recommended to patients with 2 or 3 risk factors. Author Disclosure: S. Li: None. S. Wang: None. Y. Song: None. W. Wang: None. J. Jin: None. Y. Liu: None. H. Fang: None. H. Ren: None. X. Liu: None. Z. Yu: None. Y. Li: None.
Outcome of Brain Metastases From HER 2ePositive Breast Cancer: Difference in Survival Benefit From Anti-HER 2 Treatment After WBRT With Regard to Prior Targeted Therapy J. Chen, Q. Zhang, X. Yu, Z. Zhang, and X. Guo; Fudan University, Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): Whole brain radiation therapy (WBRT) remains the standard treatment of brain metastasis (BM) from breast cancer (BC), especially in patients (pts) with multiple lesions. Post-WBRT anti-HER 2 treatment has been reported to improve overall survival (OS) in pts with BM from HER 2+ BC. Nevertheless, whether the benefit of post-WBRT anti-HER 2 treatment varies with prior targeted therapy is unclear. Current study aims to explore the benefit of post-WBRT anti-HER 2 treatment with regards to prior status of targeted therapy. Materials/Methods: A total of 60 pts with BM from HER 2-+ BC treated with WBRT in single institute between Jan.2006 and Feb.2012 was retrospectively analyzed, 46 pts (76.7%) had multiple lesions. The median age at BM was 53 yrs (28-73 yrs). The brain was the first metastatic site in 16 pts (26.7%). Post-WBRT anti-HER 2 treatment was given to 40.0% (n Z 24) of pts, 19 of them also had anti-HER 2 therapy prior to BM, in the adjuvant (n Z 7) and/or metastatic setting (n Z 16). Prognostic analysis was performed including age at BM, KPS/RPA, ER/PR status, number of BM, interval between BC diagnosis and BM, presence of extracranial metastases, extracranial metastases control, chemotherapy after WBRT and anti-HER 2 treatment after WBRT. Results: The median OS after BM in the whole group was 12 months (1-94 m). In univariate analysis, age, KPS/RPA classes, number of BM, extracranial metastases control, chemotherapy after WBRT and anti-HER 2 treatment after WBRT were significant prognostic factors for OS (p < 0.05), while in multivariate analysis, extracranial control, chemotherapy after WBRT and anti-HER 2 treatment after WBRT were significant prognostic factors for OS. OS was significantly longer in pts who received anti-HER 2 treatment after WBRT compared with pts who did not (21 vs 9 m; p Z 0.002), which was also significantly longer in pts received chemotherapy after WBRT than those who did not (16 vs 6 m; p < 0.001). The best median survival (34 m) was observed in pts who started anti-HER 2 treatment ONLY after WBRT, followed by pts (18 m) who had anti-HER 2 treatment before and after WBRT, and pts without anti-HER 2 treatment at all (9 m) (p Z 0.002). The median interval from diagnosis of BC to BM was 29.5 m (2-136 m) in the whole cohort, which was longer in pts
2076 WITHDRAWN
2077 Risk Factors for Supraclavicular Nodal Failure in Chinese Breast Cancer Patients With 1-3 Positive Axillary Nodes Treated With Breast-Conserving Surgery Without Supraclavicular Nodal Radiation S. Li, S. Wang, Y. Song, W. Wang, J. Jin, Y. Liu, H. Fang, H. Ren, X. Liu, Z. Yu, and Y. Li; Department of Radiation Therapy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China