- Email: [email protected]
Hypofractionated Radiation Therapy for Ductal Carcinoma in Situ of the Breast
S134
International Journal of Radiation Oncology Biology Physics
contrary, skin side effects occur more frequently after external beam PBI and WBI. Author Disclosure: C. Polgar: None. T. Major: None. Z. Sulyok: None. Z. Takacsi-Nagy: None. J. Fodor: None.
Pharmaceuticals for a Phase I trial (trial itself investigator-initiated and funded by BCRF not industry). K. Advisory Board; Eviti Medical Advisory Board. S. Leadership; Chair ROI Research Committee, Chair ASCO Ethics Committee. K. Griffith: None. D. Heimburger: None. E.M. Walker: None. T.P. Boike: None. I.S. Grills: None. J.M. Moran: None. J. Hayman: None. L.J. Pierce: J. In-kind Donation; Provision of drug only from Abbvie Pharmaceuticals for a Phase I trial (trial itself investigator-initiated and funded by BCRF not industry).
293 Choosing Wisely? Patterns and Correlates of the Use of Hypofractionated Whole Breast Radiation Therapy in the State of Michigan R. Jagsi,1 K. Griffith,1 D. Heimburger,2 E.M. Walker,3 T.P. Boike,4 I.S. Grills,5 J.M. Moran,1 J. Hayman,1 and L.J. Pierce1; 1University of Michigan, Ann Arbor, MI, 2Munson, Traverse City, MI, 3Henry Ford Hospital, Detroit, MI, 4McLaren Northern Michigan, Petoskey, MI, 5 Beaumont Health System, Royal Oak, MI Purpose/Objective(s): Hypofractionated whole breast radiation therapy (HRT) reduces the cost and burden of adjuvant RT for breast cancer and has equivalent outcomes to standard fractionation for appropriate patients. Recent studies have suggested that utilization of HRT is low and variable. We investigated patterns and correlates of HRT in a consortium of RT practices in Michigan to determine variation at the practice level and whether use reflects individualization based on potentially relevant patient characteristics (such as habitus, age, chemotherapy receipt, or laterality). Materials/Methods: We evaluated the proportion of whole breast RT administered with hypofractionated approaches in breast cancer patients receiving lumpectomy and RT at each practice participating in the Michigan Radiation Oncology Quality Consortium (MROQC). MROQC is an initiative that includes community and academic practices that collect detailed dosimetric, clinical, and patient-reported data on all breast cancer patients receiving adjuvant whole breast RT after lumpectomy at these sites, regardless of payor. We evaluated associations between HRT receipt and various patient characteristics. Results: Of 1475 patients registered by MROQC from October 2011 to December 2013, 919 had T1-2, N0 breast cancer. Of these 919, 284 (30.9%) received HRT, of whom 185 (72.8%) received a boost. Among the 13 practices, HRT use ranged from 2% to 80%. On multivariable analysis, HRT was more likely in patients who were older (OR Z 1.04 per 1-yr increase, p < 0.001) and less likely with larger body habitus (OR Z 0.92 per 1 cm increase in separation, p Z 0.001) and with chemotherapy receipt (OR Z 0.42, p < 0.001). Use was not significantly associated with laterality (p Z 0.17). HRT use was not higher in the last 6 months analyzed (29.5% from 6/13-12/13 vs 30.9% from 10/11-5/13; p Z 0.70). HRT use in other stage MROQC patients was 81 (26%) among 311 DCIS patients and 92 (19.8%) among 465 node-positive patients. Conclusions: HRT has been variably administered in the adjuvant setting in Michigan since the publication of the long-term results of the Canadian trial and after the initiation of the Choosing Wisely campaign. Use varies by patient characteristics but also varies substantially between practices, suggesting that differences in use may reflect differences in physician attitudes or knowledge. Oral Scientific Abstract 293; Table Variability in Hypofractionation Use Across the 9 Highest-Volume MROQC Sites Institution ID (type) 1 2 3 4 5 6 7 8 9
(academic) (community) (academic) (community) (academic) (community) (academic) (community) (community)
number of T1-2, N0 cases
Percent hypofractionated
144 123 118 97 90 89 71 40 36
39.6% 17.1% 14.4% 79.4% 21.1% 2.2% 56.3% 20.0% 11.1%
Author Disclosure: R. Jagsi: E. Research Grant; NIH, American Cancer Society, Breast Cancer Research Foundation, National Comprehensive Cancer Network. J. In-kind Donation; Provision of drug only from Abbvie
294 Hypofractionated Radiation Therapy for Ductal Carcinoma in Situ of the Breast N. Lalani,1 L. Paszat,2 R. Nofech-Mozes,3 S. Narod,4 W. Hanna,3 D. Thiruchelvam,2 A. Tuck,5 S. Sengupta,6 L. Elavathil,7 P. Jani,8 S. Done,9 N. Miller,9 B. Youngson,9 M. Bonin,10 and E. Rakovitch3; 1 University of Toronto, Toronto, ON, Canada, 2Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 4Women’s College Research Institute, Toronto, ON, Canada, 5London Health Sciences Center, London, ON, Canada, 6Kingston General Hospital, Kingston, ON, Canada, 7University Health Network, Toronto, ON, Canada, 8Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada, 9University Health Network, University of Toronto, Toronto, ON, Canada, 10Sudbury Regional Hospital, Sudbury, ON, Canada Purpose/Objective(s): The main goal of treating ductal carcinoma in situ (DCIS) is to prevent the development of recurrent breast cancer with optimal cosmesis. The addition of whole breast radiation therapy (XRT) after breast-conserving surgery (BCS) has been shown to decrease the risk of local recurrence (DCIS or invasive), but the optimal dose fractionation radiation therapy regimen remains unclear. Past randomized studies administered 50 Gray/25 fractions delivered over 5 weeks (conventional dose fractionation regimen) however, treatment pattern studies on the management of DCIS report that accelerated, hypofractionated (HF) regimens are frequently used. HF radiation therapy provides equivalent rates of local recurrence after lumpectomy for invasive breast cancer, but it is unknown if the two fractionation regimens lead to similar rates of local recurrence after BCS for DCIS. We report the impact of HF radiation therapy regimen (vs. conventional regimen) on the long-term risk of local recurrence in a population of individuals with pure DCIS treated with BCS and XRT. Materials/Methods: All women diagnosed with DCIS and treated with BCS and XRT in Ontario from 1994-2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of radiation fractionation scheme (conventional versus HF) on the development of local recurrence was determined using survival analyses. To account for systematic differences between women treated with HF versus conventional radiation schemes, we used a propensity score adjustment approach. Results: We identified 1,609 women with DCIS treated BCS and radiation. Median follow-up was 10.2 years. Median age at diagnosis was 56 years (range 49-65 years). Nine hundred seventy-one women (60%) received conventional radiation therapy regimen and 638 cases (40%) received a HF regimen. The cumulative 10-year rate of local recurrence was 12% (n Z 190). The 10 year actuarial local recurrence-free survival rate was 86% among women treated with conventional radiation therapy and 89% for those treated with HF regimen. (p Z 0.03). On multivariable analyses adjusted for propensity score, year of diagnosis and administration of boost, age < 45 years at diagnosis (HR Z 2.4, 95% CI Z 1.6-3.4, p < 0.0001), high (HR Z 2.9, 95% CI Z 1.2-7.3, p Z 0.02) or intermediate nuclear grade (HR Z 2.7, 95% CI Z 1.1-6.6, p Z 0.04) and positive resection margins (HR Z 1.4, 95% CI Z 1.0-2.1, p Z 0.05) were associated with an increased risk of local recurrence. Administration of HF radiation therapy was not significantly associated with an increased risk of local recurrence (or invasive recurrence) compared to individuals treated with conventional fractionation (HR Z 0.8, 95% CI Z 0.5-1.2, p Z 0.34).
Volume 90 Number 1S Supplement 2014
Oral Scientific Sessions S135
Conclusions: At 10 years, the risk of local recurrence among individuals treated with HF radiation therapy after BCS for pure DCIS was similar to individuals treated with conventional radiation therapy. Author Disclosure: N. Lalani: None. L. Paszat: None. R. Nofech-Mozes: None. S. Narod: None. W. Hanna: None. D. Thiruchelvam: None. A. Tuck: None. S. Sengupta: None. L. Elavathil: None. P. Jani: None. S. Done: None. N. Miller: None. B. Youngson: None. M. Bonin: None. E. Rakovitch: None.
295 Preoperative Partial Breast Radiation Therapy: One Year Outcomes and Radiation-Induced Changes in Gene Expression J.K. Horton,1 R. Blitzblau,1 S. Yoo,1 G. Georgiade,1 J. Geradts,1 J. Baker,1 J.A. Chi,1 Z. Chang,1 M. Palta,1 S. Siamakpour-Reihani,1 J. Groth,1 W. Chen,1 G. Broadwater,1 W.T. Barry,2 E. Duffy,1 and S. Hwang1; 1Duke University Medical Center, Durham, NC, 2Dana Farber Cancer Institute, Boston, NC Purpose/Objective(s): Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, many PBI techniques require equipment or skills not readily available. Furthermore, suboptimal cosmetic outcomes have been noted with external beam techniques, likely related to large post-operative treatment volumes. To address these issues, we designed a phase I protocol utilizing widely available radiation techniques to 1) evaluate patients’ tolerance of a single radiation treatment delivered preoperatively to a small-volume, intact breast tumor and 2) identify biomarkers of radiation response. Materials/Methods: Women aged 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease < 2 cm were enrolled (n Z 32). Intensity-modulated radiation therapy was used to deliver 15, 18, or 21 Gy to the tumor plus a 1.5 cm margin. Lumpectomy was performed within 10 days. Patients with high-risk pathologic features received conventional radiation (n Z 3) postoperatively. Formalin-fixed, paraffin-embedded, pre- and post-radiation patient samples were used for gene expression profiling. Gene expression in paired samples was evaluated with the RMA algorithm and the Bioconductor limma package with correction for multiple comparisons. Results: No locoregional or distant recurrences have been reported (median follow-up 12.6 months). Cosmetic outcomes are good/ excellent in all patients receiving only preoperative radiation. Chronic toxicities were primarily grade 1-2 and expected (fibrosis, breast pain, skin induration). One grade 3 toxicity (breast atrophy) occurred in a patient receiving postoperative radiation. Genes significantly induced with radiation are listed in Table 1. Specifically, genes involved in apoptosis and cell cycle control were differentially expressed in tumors after radiation. Conclusions: Preoperative single-dose radiation therapy to the intact breast tumor is efficacious and well-tolerated at one year. Genes governing radiation response, including those involved in cell cycle control and programmed cell death, may play a role in the increased radiation sensitivity observed clinically in ER+ cancers. Our groundbreaking study describes specific pathways modulated by radiation in human breast tumors. We expect this to aid in identification of therapeutic targets for biologically based radiation therapy.
Author Disclosure: J.K. Horton: E. Research Grant; NIH, Susan G. Komen, Varian Medical Systems. R. Blitzblau: None. S. Yoo: None. G. Georgiade: None. J. Geradts: None. J. Baker: None. J.A. Chi: None. Z. Chang: None. M. Palta: None. S. Siamakpour-Reihani: None. J. Groth: None. W. Chen: None. G. Broadwater: None,. W.T. Barry: None. E. Duffy: None. S. Hwang: K. Advisory Board; Genomic Health Inc.
296 Intraoperative Radiation Therapy Prior to Lumpectomy for EarlyStage Breast Cancer: A Single Institution Study L. Ma, W. Yu, Z. Ju, H. Gong, X. Li, Y. Zhang, Q. Kong, and J. Wang; Chinese PLA General Hospital, Beijing, China Purpose/Objective(s): To evaluate the safety, cosmesis, and clinical efficacy of intra-operative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. Materials/Methods: From December 2008 to March 2013, 75 breast cancer patients (ages 34 - 66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile LINAC. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by a post-operative external beam radiation therapy of 50 Gy in 25 fractions; the others had 15 Gy prescribed to the 90% isodose depth. The dose rate was 10 Gy/min. for all patients. Adjuvant treatment consisted of chemotherapy alone (14 patients), hormonal therapy alone (18 patients), or combined chemotherapy and hormonal therapy (41 patients). Two patients had no adjuvant treatment. The safety, cosmesis, and short-term efficacy were evaluated. Results: Median follow-up was 49 months (range: 19 - 58 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.5%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.4%. No distant metastasis or death was observed. The 3-year disease free survival rate was 94.2%. Conclusions: IORT delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of late side effects and long-term efficacy. Author Disclosure: L. Ma: None. W. Yu: None. Z. Ju: None. H. Gong: None. X. Li: None. Y. Zhang: None. Q. Kong: None. J. Wang: None.
297 Outcomes of “Unsuitable” Patients by ASTRO Guidelines Treated with Accelerated Partial Breast Irradiation via Interstitial Multicatheter Brachytherapy: A Multi-institution Collaborative Study P.Y. Chen,1 M. Kamrava,2 R. Kuske,3 B.M. Anderson,4 J.K. Hayes,5 J. DeManes,6 P. Wang,6 P. Wang,6 D. Veruttipong,6 and M. Snyder3; 1 Oakland U-Wm Beaumont School of Medicine, Beaumont Health System, Royal Oak, MI, 2UCLA Radiation Oncology, Los Angeles, CA, 3Arizona
Oral Scientific Abstract 295; Table Gene
Probe Set (#)
FDR adjusted p value
Protein Family
Function
NR4A1 MDM2 DUSP1 CDKN1A EGR1 GDF15 FOS FOSB SRGN
6 4 4 2 2 2 1 1 1
0.0230 0.0239 0.0218 0.0020 0.0230 0.0236 0.0190 0.0236 0.0239
Nuclear hormone receptor Regulatory enzyme Phosphatase Cyclin-dependent kinase Transcription factor Growth factor Transcription factor Transcription factor Serglycin
Apoptosis Cell cycle checkpoint/p53 MAPK signal transduction Cell cycle/p53 Proliferation Differentiation/p53 Cell proliferation/apoptosis Cell proliferation/anti-apoptosis Apoptosis
International Journal of Radiation Oncology Biology Physics
contrary, skin side effects occur more frequently after external beam PBI and WBI. Author Disclosure: C. Polgar: None. T. Major: None. Z. Sulyok: None. Z. Takacsi-Nagy: None. J. Fodor: None.
Pharmaceuticals for a Phase I trial (trial itself investigator-initiated and funded by BCRF not industry). K. Advisory Board; Eviti Medical Advisory Board. S. Leadership; Chair ROI Research Committee, Chair ASCO Ethics Committee. K. Griffith: None. D. Heimburger: None. E.M. Walker: None. T.P. Boike: None. I.S. Grills: None. J.M. Moran: None. J. Hayman: None. L.J. Pierce: J. In-kind Donation; Provision of drug only from Abbvie Pharmaceuticals for a Phase I trial (trial itself investigator-initiated and funded by BCRF not industry).
293 Choosing Wisely? Patterns and Correlates of the Use of Hypofractionated Whole Breast Radiation Therapy in the State of Michigan R. Jagsi,1 K. Griffith,1 D. Heimburger,2 E.M. Walker,3 T.P. Boike,4 I.S. Grills,5 J.M. Moran,1 J. Hayman,1 and L.J. Pierce1; 1University of Michigan, Ann Arbor, MI, 2Munson, Traverse City, MI, 3Henry Ford Hospital, Detroit, MI, 4McLaren Northern Michigan, Petoskey, MI, 5 Beaumont Health System, Royal Oak, MI Purpose/Objective(s): Hypofractionated whole breast radiation therapy (HRT) reduces the cost and burden of adjuvant RT for breast cancer and has equivalent outcomes to standard fractionation for appropriate patients. Recent studies have suggested that utilization of HRT is low and variable. We investigated patterns and correlates of HRT in a consortium of RT practices in Michigan to determine variation at the practice level and whether use reflects individualization based on potentially relevant patient characteristics (such as habitus, age, chemotherapy receipt, or laterality). Materials/Methods: We evaluated the proportion of whole breast RT administered with hypofractionated approaches in breast cancer patients receiving lumpectomy and RT at each practice participating in the Michigan Radiation Oncology Quality Consortium (MROQC). MROQC is an initiative that includes community and academic practices that collect detailed dosimetric, clinical, and patient-reported data on all breast cancer patients receiving adjuvant whole breast RT after lumpectomy at these sites, regardless of payor. We evaluated associations between HRT receipt and various patient characteristics. Results: Of 1475 patients registered by MROQC from October 2011 to December 2013, 919 had T1-2, N0 breast cancer. Of these 919, 284 (30.9%) received HRT, of whom 185 (72.8%) received a boost. Among the 13 practices, HRT use ranged from 2% to 80%. On multivariable analysis, HRT was more likely in patients who were older (OR Z 1.04 per 1-yr increase, p < 0.001) and less likely with larger body habitus (OR Z 0.92 per 1 cm increase in separation, p Z 0.001) and with chemotherapy receipt (OR Z 0.42, p < 0.001). Use was not significantly associated with laterality (p Z 0.17). HRT use was not higher in the last 6 months analyzed (29.5% from 6/13-12/13 vs 30.9% from 10/11-5/13; p Z 0.70). HRT use in other stage MROQC patients was 81 (26%) among 311 DCIS patients and 92 (19.8%) among 465 node-positive patients. Conclusions: HRT has been variably administered in the adjuvant setting in Michigan since the publication of the long-term results of the Canadian trial and after the initiation of the Choosing Wisely campaign. Use varies by patient characteristics but also varies substantially between practices, suggesting that differences in use may reflect differences in physician attitudes or knowledge. Oral Scientific Abstract 293; Table Variability in Hypofractionation Use Across the 9 Highest-Volume MROQC Sites Institution ID (type) 1 2 3 4 5 6 7 8 9
(academic) (community) (academic) (community) (academic) (community) (academic) (community) (community)
number of T1-2, N0 cases
Percent hypofractionated
144 123 118 97 90 89 71 40 36
39.6% 17.1% 14.4% 79.4% 21.1% 2.2% 56.3% 20.0% 11.1%
Author Disclosure: R. Jagsi: E. Research Grant; NIH, American Cancer Society, Breast Cancer Research Foundation, National Comprehensive Cancer Network. J. In-kind Donation; Provision of drug only from Abbvie
294 Hypofractionated Radiation Therapy for Ductal Carcinoma in Situ of the Breast N. Lalani,1 L. Paszat,2 R. Nofech-Mozes,3 S. Narod,4 W. Hanna,3 D. Thiruchelvam,2 A. Tuck,5 S. Sengupta,6 L. Elavathil,7 P. Jani,8 S. Done,9 N. Miller,9 B. Youngson,9 M. Bonin,10 and E. Rakovitch3; 1 University of Toronto, Toronto, ON, Canada, 2Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 4Women’s College Research Institute, Toronto, ON, Canada, 5London Health Sciences Center, London, ON, Canada, 6Kingston General Hospital, Kingston, ON, Canada, 7University Health Network, Toronto, ON, Canada, 8Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada, 9University Health Network, University of Toronto, Toronto, ON, Canada, 10Sudbury Regional Hospital, Sudbury, ON, Canada Purpose/Objective(s): The main goal of treating ductal carcinoma in situ (DCIS) is to prevent the development of recurrent breast cancer with optimal cosmesis. The addition of whole breast radiation therapy (XRT) after breast-conserving surgery (BCS) has been shown to decrease the risk of local recurrence (DCIS or invasive), but the optimal dose fractionation radiation therapy regimen remains unclear. Past randomized studies administered 50 Gray/25 fractions delivered over 5 weeks (conventional dose fractionation regimen) however, treatment pattern studies on the management of DCIS report that accelerated, hypofractionated (HF) regimens are frequently used. HF radiation therapy provides equivalent rates of local recurrence after lumpectomy for invasive breast cancer, but it is unknown if the two fractionation regimens lead to similar rates of local recurrence after BCS for DCIS. We report the impact of HF radiation therapy regimen (vs. conventional regimen) on the long-term risk of local recurrence in a population of individuals with pure DCIS treated with BCS and XRT. Materials/Methods: All women diagnosed with DCIS and treated with BCS and XRT in Ontario from 1994-2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of radiation fractionation scheme (conventional versus HF) on the development of local recurrence was determined using survival analyses. To account for systematic differences between women treated with HF versus conventional radiation schemes, we used a propensity score adjustment approach. Results: We identified 1,609 women with DCIS treated BCS and radiation. Median follow-up was 10.2 years. Median age at diagnosis was 56 years (range 49-65 years). Nine hundred seventy-one women (60%) received conventional radiation therapy regimen and 638 cases (40%) received a HF regimen. The cumulative 10-year rate of local recurrence was 12% (n Z 190). The 10 year actuarial local recurrence-free survival rate was 86% among women treated with conventional radiation therapy and 89% for those treated with HF regimen. (p Z 0.03). On multivariable analyses adjusted for propensity score, year of diagnosis and administration of boost, age < 45 years at diagnosis (HR Z 2.4, 95% CI Z 1.6-3.4, p < 0.0001), high (HR Z 2.9, 95% CI Z 1.2-7.3, p Z 0.02) or intermediate nuclear grade (HR Z 2.7, 95% CI Z 1.1-6.6, p Z 0.04) and positive resection margins (HR Z 1.4, 95% CI Z 1.0-2.1, p Z 0.05) were associated with an increased risk of local recurrence. Administration of HF radiation therapy was not significantly associated with an increased risk of local recurrence (or invasive recurrence) compared to individuals treated with conventional fractionation (HR Z 0.8, 95% CI Z 0.5-1.2, p Z 0.34).
Volume 90 Number 1S Supplement 2014
Oral Scientific Sessions S135
Conclusions: At 10 years, the risk of local recurrence among individuals treated with HF radiation therapy after BCS for pure DCIS was similar to individuals treated with conventional radiation therapy. Author Disclosure: N. Lalani: None. L. Paszat: None. R. Nofech-Mozes: None. S. Narod: None. W. Hanna: None. D. Thiruchelvam: None. A. Tuck: None. S. Sengupta: None. L. Elavathil: None. P. Jani: None. S. Done: None. N. Miller: None. B. Youngson: None. M. Bonin: None. E. Rakovitch: None.
295 Preoperative Partial Breast Radiation Therapy: One Year Outcomes and Radiation-Induced Changes in Gene Expression J.K. Horton,1 R. Blitzblau,1 S. Yoo,1 G. Georgiade,1 J. Geradts,1 J. Baker,1 J.A. Chi,1 Z. Chang,1 M. Palta,1 S. Siamakpour-Reihani,1 J. Groth,1 W. Chen,1 G. Broadwater,1 W.T. Barry,2 E. Duffy,1 and S. Hwang1; 1Duke University Medical Center, Durham, NC, 2Dana Farber Cancer Institute, Boston, NC Purpose/Objective(s): Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, many PBI techniques require equipment or skills not readily available. Furthermore, suboptimal cosmetic outcomes have been noted with external beam techniques, likely related to large post-operative treatment volumes. To address these issues, we designed a phase I protocol utilizing widely available radiation techniques to 1) evaluate patients’ tolerance of a single radiation treatment delivered preoperatively to a small-volume, intact breast tumor and 2) identify biomarkers of radiation response. Materials/Methods: Women aged 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease < 2 cm were enrolled (n Z 32). Intensity-modulated radiation therapy was used to deliver 15, 18, or 21 Gy to the tumor plus a 1.5 cm margin. Lumpectomy was performed within 10 days. Patients with high-risk pathologic features received conventional radiation (n Z 3) postoperatively. Formalin-fixed, paraffin-embedded, pre- and post-radiation patient samples were used for gene expression profiling. Gene expression in paired samples was evaluated with the RMA algorithm and the Bioconductor limma package with correction for multiple comparisons. Results: No locoregional or distant recurrences have been reported (median follow-up 12.6 months). Cosmetic outcomes are good/ excellent in all patients receiving only preoperative radiation. Chronic toxicities were primarily grade 1-2 and expected (fibrosis, breast pain, skin induration). One grade 3 toxicity (breast atrophy) occurred in a patient receiving postoperative radiation. Genes significantly induced with radiation are listed in Table 1. Specifically, genes involved in apoptosis and cell cycle control were differentially expressed in tumors after radiation. Conclusions: Preoperative single-dose radiation therapy to the intact breast tumor is efficacious and well-tolerated at one year. Genes governing radiation response, including those involved in cell cycle control and programmed cell death, may play a role in the increased radiation sensitivity observed clinically in ER+ cancers. Our groundbreaking study describes specific pathways modulated by radiation in human breast tumors. We expect this to aid in identification of therapeutic targets for biologically based radiation therapy.
Author Disclosure: J.K. Horton: E. Research Grant; NIH, Susan G. Komen, Varian Medical Systems. R. Blitzblau: None. S. Yoo: None. G. Georgiade: None. J. Geradts: None. J. Baker: None. J.A. Chi: None. Z. Chang: None. M. Palta: None. S. Siamakpour-Reihani: None. J. Groth: None. W. Chen: None. G. Broadwater: None,. W.T. Barry: None. E. Duffy: None. S. Hwang: K. Advisory Board; Genomic Health Inc.
296 Intraoperative Radiation Therapy Prior to Lumpectomy for EarlyStage Breast Cancer: A Single Institution Study L. Ma, W. Yu, Z. Ju, H. Gong, X. Li, Y. Zhang, Q. Kong, and J. Wang; Chinese PLA General Hospital, Beijing, China Purpose/Objective(s): To evaluate the safety, cosmesis, and clinical efficacy of intra-operative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. Materials/Methods: From December 2008 to March 2013, 75 breast cancer patients (ages 34 - 66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile LINAC. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by a post-operative external beam radiation therapy of 50 Gy in 25 fractions; the others had 15 Gy prescribed to the 90% isodose depth. The dose rate was 10 Gy/min. for all patients. Adjuvant treatment consisted of chemotherapy alone (14 patients), hormonal therapy alone (18 patients), or combined chemotherapy and hormonal therapy (41 patients). Two patients had no adjuvant treatment. The safety, cosmesis, and short-term efficacy were evaluated. Results: Median follow-up was 49 months (range: 19 - 58 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.5%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.4%. No distant metastasis or death was observed. The 3-year disease free survival rate was 94.2%. Conclusions: IORT delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of late side effects and long-term efficacy. Author Disclosure: L. Ma: None. W. Yu: None. Z. Ju: None. H. Gong: None. X. Li: None. Y. Zhang: None. Q. Kong: None. J. Wang: None.
297 Outcomes of “Unsuitable” Patients by ASTRO Guidelines Treated with Accelerated Partial Breast Irradiation via Interstitial Multicatheter Brachytherapy: A Multi-institution Collaborative Study P.Y. Chen,1 M. Kamrava,2 R. Kuske,3 B.M. Anderson,4 J.K. Hayes,5 J. DeManes,6 P. Wang,6 P. Wang,6 D. Veruttipong,6 and M. Snyder3; 1 Oakland U-Wm Beaumont School of Medicine, Beaumont Health System, Royal Oak, MI, 2UCLA Radiation Oncology, Los Angeles, CA, 3Arizona
Oral Scientific Abstract 295; Table Gene
Probe Set (#)
FDR adjusted p value
Protein Family
Function
NR4A1 MDM2 DUSP1 CDKN1A EGR1 GDF15 FOS FOSB SRGN
6 4 4 2 2 2 1 1 1
0.0230 0.0239 0.0218 0.0020 0.0230 0.0236 0.0190 0.0236 0.0239
Nuclear hormone receptor Regulatory enzyme Phosphatase Cyclin-dependent kinase Transcription factor Growth factor Transcription factor Transcription factor Serglycin
Apoptosis Cell cycle checkpoint/p53 MAPK signal transduction Cell cycle/p53 Proliferation Differentiation/p53 Cell proliferation/apoptosis Cell proliferation/anti-apoptosis Apoptosis