Prognostic Factors and Local Recurrence Pattern in Breast Phyllodes Tumors: A Nomogram Based on Retrospective Cohort Study of 404 Cases

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International Journal of Radiation Oncology  Biology  Physics

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g-H2AX foci detection by immunofluorescence assay showed that the

Additional Surgeries After Breast Reconstruction in Patients With Breast Cancer Undergoing Mastectomy L. Zhang, X. Yu, Z. Yang, X. Chen, X. Wang, J. Luo, J. Wu, and X.M. Guo; Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective(s): Breast reconstruction can greatly improve the quality of life for patients with breast cancer who have undergone mastectomy. However, additional surgeries after the initial reconstruction potentially reduce the quality of life and increase healthcare utilization. The purpose of this study was to determine the reoperation rates following breast reconstruction in patients with breast cancer who have undergone mastectomy. Materials/Methods: Between June 2001 and December 2013, 661 breast cancer patients treated with mastectomy and breast reconstruction with/ without radiation therapy were analyzed retrospectively. Reoperations were categorized into three types: Anticipated: expected component of the reconstruction process, such as operations to replace a temporary expander with a permanent implant, a nipple reconstruction or a contralateral balancing operation; Unanticipated: operations to treat complications after breast reconstruction at breast or donor site; Others: operations unrelated to breast reconstruction, such as contralateral breast cancer or other secondary primary cancer surgeries, operations to treat recurrences. The reoperation rates and types after the initial breast reconstruction was analyzed. Results: A total of 940 operations were done for these 661 breast cancer patients with an median follow-up of 46.3 months. 228 (34.5%) patients underwent at least one reoperation after the initial breast reconstruction. The median number of reoperations per patient was 1 (range, 1 to 4). Patients had their second surgery within 8.9 months of reconstruction(range, 1 to 127 months). The majority of additional operations was expected component of the reconstruction process (55.8%). 13.8% and 30.4% of reoperations were to treat complications or unrelated to breast reconstruction. Conclusion: A considerable amount of patients underwent additional surgeries after the initial breast reconstruction and the majority of reoperations were related to reconstruction. This should be taken into consideration when choosing breast reconstruction. Author Disclosure: L. Zhang: None. X. Yu: None. Z. Yang: None. X. Chen: None. X. Wang: None. J. Luo: None. J. Wu: None. X. Guo: None.

2140 Radiosensitivity Effect and Regulatory Mechanisms of PARP-1 Inhibitors on Brca Mutant Breast Cancer W. Zhao,1 L. Li,2 and X. Zhu2; 1Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, China, 2 Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, China Purpose/Objective(s): To investigate the radiosensitivity effect of poly ADP-ribose polymerase -1 (PARP-1) inhibitor 3-amion benzamide (3-AB) on the BRCA non-mutant and BRCA mutant breast cancer cells, and to demonstrate the role and regulatory mechanism of PARP-1 and BRCA gene in radiation-induced DNA damage repair. Materials/Methods: The MDA-MB-436 cells and MDA-MB-231 cells were divided into four groups respectively as the control (CTRL), ionizing radiation alone(IR), 3-AB alone(3-AB), ionizing radiation combined with 3-AB（IR+3-AB）group. The g-H2AX foci detection by immunofluorescence assay was applied to detect the DNA double-strand damage. The radiosensitivity of breast cancer cells was evaluated by clonogenic cell survival assays, and the percentage of apoptotic cells was assessed by flow cytometry. Results: The MDA-MB-436 cells, compared with MDA-MB-231 cells, was significantly increased, and 3-AB could further enhance the effect.

double-stranded damage of the MDA-MB-436 cells was significantly more than that of MDA-MB-231 cells (tZ4.57, P<0.05). 3-AB could further enhance the effect, and the DNA damage of HCC1973 cells in the IR+3AB group was the most remarkable, the difference was statistically significant(tZ3.26, P<0.05). Flow cytometry showed that the cells in the IR+3-AB group had the highest rate of apoptosis（tZ3.81, P＜0.05）. The apoptosis rate of MDA-MB-436 cells was significantly increased compared with MDA-MB-231 cells（tZ2.96, P<0.05） Conclusion: The DNA damage induced by radiation and the radiosensetivity of BRCA mutant cells MDA-MB-436 is significantly increased than that of non-BRCA mutant cells MDA-MB-231. The inhibitor of DNA single-strand damage repair gene PARP-1 can further increase the apoptosis and radiosensitivity of BRCA-mutant cells by further blocking the repair of single-strand damage induced by ionizing radiation. Author Disclosure: W. Zhao: None. L. Li: None. X. Zhu: None.

2141 Acute and Late Toxicity of Uniform Scanning Proton Therapy for Breast Cancer Patients Y. Zheng,1 K. Prabhu Jr,2 G.L. Larson,3 and C.E. Vargas4; 1Atlantic Health System, Morristown, NJ, 2Radiation Medicine Associates, Oklahoma City, OK, 3ProCure Proton Therapy Center, Oklahoma City, OK, 4Mayo Clinic, Phoenix, AZ Purpose/Objective(s): To analyze the acute and late toxicity and patterns of failure of uniform scanning proton therapy for breast cancer patients. Materials/Methods: We analyzed 100 breast cancer patients treated at our center. Each patient was treated with uniform scanning proton beams, using typically 2-4 anterior oblique and/or lateral fields. The prescription was 45-50.4 Cobalt gray equivalent (CGE) at 1.8 CGE/ fraction and followed by a 9-16.2 CGE boost treatment as needed. Toxicity types and frequencies were obtained from the Proton Collaborative Group (PCG) registry trial (REG001-09) and analyzed. In addition, skin reaction was carefully studied by analyzing photos of treatment surface, which were taken every 5 fractions during proton therapy. Late toxicity data was based on follow up at least six months after completion of treatment. Results: No patients experienced Grade 4 or 5 toxicity. The most common acute adverse effect was dermatitis (Grade 1, 31%%; Grade 2, 52%, Grade 3, 6%), followed by skin discomfort, hot flashes, fatigue, cough, breast pain, chest wall pain, lymphedema and nipple deformation. Other toxicities such as esophagitis were infrequent, with an incidence rate of 2% or lower. Late toxicities post treatment were relatively rare, mainly included hot flashes (3%), arthralgia (2%), lymphedema (2%), nipple deformity (2%), breast pain (1%) and brachial plexopathy (1%). Other than two cases with Grade 2 hot flashes, all late toxicities were Grade 1. Conclusion: Dermatitis and discomfort were the top two acute toxicities in terms of frequency and severity. However, no Grade 4 or above was observed, and other toxicities were of Grade 2 or less. Late toxicities such as hot flashes and nipple deformation were relatively rare (<3%) and of Grade 2 or lower. Overall, uniform scanning proton therapy was well tolerated for breast cancer treatment. Author Disclosure: Y. Zheng: None. K. Prabhu: None. G.L. Larson: board member; ProCure OKC. C.E. Vargas: Stock; View Ray. ; Proton Collaborative Group.

2142 Prognostic Factors and Local Recurrence Pattern in Breast Phyllodes Tumors: A Nomogram Based on Retrospective Cohort Study of 404 Cases Z. Zhou, C.C. Wang, X.J. Sun, Z. Yang, X. Chen, X. Yu, and X.M. Guo; Fudan University Shanghai Cancer Center, Shanghai, China

Volume 99  Number 2S  Supplement 2017 Purpose/Objective(s): This study investigate the effect of clinico-pathologic features, surgical approaches, and adjuvant radiotherapy on prognosis and to explore independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). Materials/Methods: A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. The relationship of clinico-pathologic features, surgical treatment, and adjuvant radiotherapy with prognosis was analyzed. According to their histological type, benign PTBs were classified as a low-risk group while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups and a nomogram was made to predict recurrence-free survival at 1, 3 and 5 years. Results: Of the 404 patients, 168 (41.6%) had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including 6 benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group while surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, patients received simple excision and with infiltrative tumor border have a higher recurrence rate. A nomogram developed based on clinico-pathologic features and surgical approaches could predict recurrence-free survival at 1, 3 and 5 years. Conclusion: Histological grade and degree of stromal malignancy were closely associated with postoperative local recurrence of PTB. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, and degree of stromal cell hyperplasia and atypia can be applied for patient counselling and clinical management. The efficacy of adjuvant radiotherapy is still uncertain. Author Disclosure: Z. Zhou: None. C. Wang: None. X. Sun: None. Z. Yang: None. X. Chen: None. X. Yu: None. X. Guo: None.

2143 Evaluation of Single Fraction High-Gradient Partial Breast Irradiation as the Sole Method of Radiation Therapy for Low-Risk Stage 0 and I Breast CancerdEarly Results of a Single Institution Prospective Clinical Trial I. Zoberi, M.A. Thomas, and L.L. Ochoa; Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO Purpose/Objective(s): To test the hypothesis that a single fraction of external beam radiotherapy to breast tissue one centimeter around a partial mastectomy cavity will result in acceptable ipsilateral breast tumor recurrence rates, tolerance, and cosmesis in select women with low-risk early stage breast cancer. Materials/Methods: Postmenopausal women undergoing breast conserving surgery for breast cancers less than or equal to 2 cm in size were enrolled in a single institution prospective clinical trial. Patients had to be at least 50 years old and have estrogen receptor positive cancers without her2/neu gene amplification. Radiotherapy was administered with MR-guided teletherapy except in cases were MR was contraindicated in the outpatient setting within 8 weeks of surgery. Surgical margins were required to be negative by at least 2 mm. A dose of 20 Gy was prescribed to a planning target volume (PTV) defined as the surgical cavity truncated as least 5 mm from the skin surface while simultaneously prescribing a dose of 7 Gy to the surface of a PTV defined as a 1 cm expansion of the surgical cavity in breast tissue truncated 5 mm from the skin surface. The resulting high-gradient treatment was administered in a single fraction as the sole radiotherapy treatment.

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Results: To date 19 of a planned total fifty women have been treated. The mean age was 64 years. Three patients had pTisN0, 10 pT1bN0, and 6 pT1cN0 disease. MR-guided teletherapy via Cobalt-60 was used in all but one patient who had a pacemaker. With a mean and median follow up time of 10.3 and 10 months from diagnosis there have been no breast cancer recurrences and no intercurrent deaths. No patient has been lost to follow up. All toxicities have been grade 1 with six patients having skin hyperpigmentation in the treatment region and three having transient breast pain. Cosmesis has remained excellent in all patients. Conclusion: Early results of our trial demonstrate that a single fraction of high-gradient radiotherapy is well tolerated. Continued enrollment and follow up is needed to determine cancer control outcomes. Author Disclosure: I. Zoberi: Employee; Washington University. M.A. Thomas: None. L.L. Ochoa: None.

2144 Comparison of Radiation Necrosis in Adult Cranial Oligodendrogliomas and Astrocytomas Treated With Proton Versus Photon Therapy S. Acharya,1 C.G. Robinson,2 J.M. Michalski,3 D. Mullen,4 C. Tsien,5 K. Rich,6 J.L. Campian,7 A. Chundury,8 S.M. Perkins,2 D.E. Hallahan,6 J.D. Bradley,2 and J. Huang2; 1Washington University in St. Louis, Department of Radiation Oncology, St. Louis, MO, 2Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO, 3 Washington University School of Medicine, St. Louis, MO, 4Washington University in St. Louis, Saint Louis, MO, 5Washington University St Louis, St Louis, MO, 6Washington University, St. Louis, MO, 7Washington University in St. Louis, Department of Medical Oncology, St. Louis, MO, 8 Department of Radiation Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): Proton therapy is a promising treatment modality for gliomas; however, data on late effects remain limited. The purpose of this study is to compare the incidence of and risk factors for clinically significant radiation necrosis (cRN) in adult cranial oligodendrogliomas and astrocytomas treated with proton versus photon therapy. Materials/Methods: Between 2007 and 2015, 160 adult patients with grade II or III oligodendroglioma or astrocytoma were treated with proton (nZ37) or photon (nZ123) therapy with or without concurrent/ sequential chemotherapy at a single institution. Proton therapy was initiated in 2014. Tumor histology was defined using 2016 World Health Organization classification. cRN was defined as symptomatic RN or asymptomatic RN that resulted in surgery or bevacizumab administration. cRN was ascertained based on all available clinical data and confirmed by a panel of 3 radiation oncologists blinded from treatment modality and radiation dose. Cumulative incidence was calculated using competing risks. Risk factors were identified using Cox proportional hazards. Results: Median follow up was 28.5 months. Median prescription dose was 5940 cGy (range: 5040-6300 cGy). 53 patients (33%) had 1p19qcodeleted oligodendroglioma and 107 patients (67%) had non-codeleted astrocytoma. Eighteen patients developed cRN (protonZ6, photonZ12). Median time to cRN was 11 months (range: 2.8e34.2 months). There was no significant difference in two-year cumulative incidence of cRN between proton and photon therapy (18.7 vs. 9.7%; 95% Confidence Interval [CI]: 7.5-33.8% vs. 5.1-16%; pZ0.16). Proton was not a significant risk factor for cRN compared to photon (Hazard Ratio [HR]: 1.81, 95% CI: 0.67e4.9, pZ0.24). On multivariate analysis, risk factors for cRN included oligodendroglioma compared to astrocytoma (HR: 3.57, 95% CI: 1.38 e 9.25, pZ0.009) and prescription dose (Gy) (HR: 1.30, 95% CI: 1.05 e 1.61, pZ0.015). The two-year cumulative incidence of cRN in oligodendrogliomas was almost four-fold that of astrocytomas (23.4 vs. 6.2%, 95% CI: 12.4-