I. J. Radiation Oncology d Biology d Physics
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Volume 81, Number 2, Supplement, 2011
Conclusions: It appears that BMI may be an important variable in determining outcome among premenopausal patients and those with hormone receptor positive DCIS treated with lumpectomy and RT. These observations require further study in a prospective fashion on larger population of patients with longer follow up. Reference: 1. Sparano et al SABCS Abs, 52-1 SABCS 2010. Author Disclosure: M. Chadha: None. S. Boolbol: None. K. Boachie-Adjei: None. L. Kirstein: None. J. Portenoy: None. L. Harrison: None.
2014
Triple Negative but not HER2 Positive Breast Cancer Subtype is Associated with Higher Locoregional Recurrence after Breast-conserving Therapy and Modern Systemic Therapy
C. Takita1, I. Reis2, F. Miao2, K. LaFave1, V. Gunaseelan1, J. L. Wright1 1
Radiation Oncology, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL, 2Biostatistics Department, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL Purpose/Objective(s): Triple negative (basal) and HER2 positive subtypes have been associated with increased risk of locoregional recurrence (LRR) in earlier studies of breast conserving therapy (BCT), in which fewer patients received systemic therapy compared with recent standards, including HER2-targeted therapy. The goal of this study is to determine whether basal and HER2+ subtypes are independent prognostic factors for LRR in BCT patients treated with modern systemic therapy. Materials/Methods: We retrospectively studied 415 patients with invasive breast cancer who received breast-conserving surgery and radiation (RT) from 1992 to 2009. Axillary surgery (sentinel node biopsy +/- dissection) was done in 404 patients (97%). Forty eight percent of patients received chemotherapy (anthracycline/taxane 34%, trastuzumab-containing 4%, other 10%). Hormonal therapy was given in 67%. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Rate of LRR was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Fine & Gray’s test. Results: Median follow-up was 60 months. Median age was 54 (26 - 86). Stage: T1 70%, T2 26.3%, T3 8%; N0 75%, N1 23.5%, N2 1.7%. Receptor status was available in 301 patients to approximate subtypes as follows: 66% Luminal A (ER or PR+/HER2 negative), 9% Luminal B (ER or PR+/HER2+), 5% HER2 (ER and PR negative/HER2+), 20% Basal (ER/PR/HER2 negative). Overall, there were 11 LRR, 15 distant metastasis, and 20 deaths. The 10-year PFS and OS were 85.4% and 90.5%, respectively. The 5 and 10-year cumulative incidence of LRR were 2.8% (95% CI: 1.4 – 5.2) and 4.5% (95% CI: 2.2 - 8.2) respectively. At 5 and 10-years, the cumulative incidence of distant metastasis (DM) was 3.0% (95% CI: 1.4 – 5.4) and 4.0% (95%CI: 2.1 - 6.9) respectively. On univariate analysis, Basal vs. Luminal A (HR: 9.12, p \ 0.001) and tumor size .2 cm vs. #2 cm (HR: 4.00, p = 0.022) were significant prognostic factors for LRR as first failure. On multivariate analysis, only basal subtype (HR: 6.29, p = 0.011) retained significance; the effects of race, menopause, luminal B/HER2 combined subtypes, tumor size, and nodal status were not significant. None of the factors tested were significant with respect to DM as first failure. Conclusions: Long-term clinical outcomes were excellent in this large cohort of early stage breast cancer patients treated with BCT and modern systemic therapy, with 10-year LRR 4.5% and OS 90.5%. Basal subtype was an independent predictor for LRR suggesting a need for better treatment strategies. Conversely, HER2+ subtype was not associated with increase in LRR, in this cohort treated with BCT and trastuzumab based-chemotherapy. Author Disclosure: C. Takita: None. I. Reis: None. F. Miao: None. K. LaFave: None. V. Gunaseelan: None. J.L. Wright: None.
2015 2016
WITHDRAWN
Mature Follow-up Low-dose Rate Interstitial Brachytherapy (LDR) following Ipsilateral Breast Tumor Recurrence (IBTR) In Patients Initially Treated with Breast Conservation Therapy: The Allegheny General Hospital Experience
M. Trombetta, T. B. Julian, E. Werts, Y. Kim, D. Parda Allegheny General Hospital, Pittsburgh, PA Purpose/Objective(s): To evaluate our mature follow-up data in women who have developed IBTR following conservation surgery and post-operative external radiotherapy retreated by lumpectomy followed by LDR in lieu of salvage mastectomy. Materials/Methods: Between 1/1998 and 10/2006, twenty-two patients with TIS or T1 IBTR were offered interstitial LDR following tumor re-excision as an alternative to salvage mastectomy. All patients had an initial lumpectomy followed by standard postoperative external beam radiotherapy [range 5000-6480cGy including boost]. Six recurred as ductal carcinoma in situ, two as infiltrating lobular carcinoma (one with a DCIS component), and fourteen as recurrent invasive carcinoma (four with a DCIS component). The recurrent tumors were excised with final margins of resection free of residual disease per National Surgical Adjuvant Breast and Bowel Project (NSABP) definition. Tumor bed implantation was then carried out with an interstitial technique utilizing 192Iridium with the target volume consisting of the tumor bed plus a minimum 1.0 centimeter clinical margin. Results: With a mean follow up of 67.5 months (range 17-115 months) Twenty-one of twenty-two patients maintained local control at the time of last follow-up or at the time of their death. The single patient who developed a second local recurrence was treated successfully with simple mastectomy. Three patients succumbed to systemic disease at 17 and 24 months after salvage implant therapy. Three patients died from unrelated causes. One patient was lost to follow-up after three years. One patient developed a contralateral breast cancer. Long-term cosmetic results as defined by the Harvard cosmesis scale (13 grade I, 6 grade II,
Proceedings of the 53rd Annual ASTRO Meeting 3 grade III) and the Allegheny General modification (which accounts for the initial cosmetic appearance) the score worsened in only 4 patients. Conclusions: These long-term data suggest that lumpectomy followed by LDR is feasible and may be an acceptable alternative to salvage mastectomy in patients for whom initial breast conservative therapy has failed. The Allegheny General Modification score better represents the long-term cosmetic effects of retreatment. Author Disclosure: M. Trombetta: None. T.B. Julian: None. E. Werts: None. Y. Kim: None. D. Parda: None.
2017
KORTUC II - A New Image-guided, Enzyme-targeted, and Breast Cancer Stem Cell Targeted Radiosensitization Treatment for Patients with Stage I and II Breast Cancers
Y. Ogawa, K. Kubota, M. Tadokoro, T. Yamanishi, N. Aoyama, Y. Suzuki, H. Iwasa, S. Kariya, M. Nogami, A. Nishioka Kochi Medical School, Nankoku 7838505, Japan Purpose/Objective(s): Tumor tissue can be re-oxygenated by inactivating peroxidase/catalase in the tumor tissue through application of hydrogen peroxide (H2O2), as H2O2 in turn is then degraded to produce oxygen. In this way, radioresistant tumors can be transformed into radiosensitive tumors. The purpose of the study was to establish a non-surgical breast conservation treatment (BCT) by utilizing a novel KORTUC radiosensitization treatment. Materials/Methods: A new radiosensitizing agent containing H2O2 and sodium hyaluronate has been developed for intra-tumoral injection in various tumors which are not superficially exposed. The agent is composed of 0.5% H2O2 and 0.83% sodium hyaluronate (CD44 molecule). Sodium hyaluronate mixed with H2O2 attaches to CD44-positive tumor cells, cells which are generally reported to be breast cancer stem cells. This new method, named KORTUC II, was approved by our local ethics committee for treatment of breast cancers and metastatic lymph nodes. A total of 40 early stage breast cancer patients (stage I: 26 patients and stage II: 14) were enrolled in the KORTUC II trial upon fully informed consent. A maximum of 6 ml of the agent was injected into breast tumor tissue twice a week under ultrasound guidance. Concerning radiation therapy, hypofraction radiotherapy was given using a tangential field approach; energy level was 4 MV and the total radiation therapy dose was 44 Gy administered as 2.75 Gy/ fraction. An electron boost of 3 Gy was added 3 times just following the 14th, 15th, and 16th administrations of 4 MV X-ray irradiation. From a needle biopsy specimen, CD44 receptor was also examined by immunohistochemistry. Results: Treatment was well tolerated with a minimum of adverse effects in all 40 patients. All of the patients achieved clinically complete response. The patients did not show any complications (with the exception of mild dermatitis), and cosmetic results were excellent for 36 patients. Patients under 75 years old with stage II breast cancer underwent systemic chemotherapy (EC and/or Taxan) prior to the KORTUC II treatment, and 32 patients with estrogen receptor-positive tumors also undertook hormonal therapy following KORTUC II. The mean follow-up period at the end of February 2011 was 28.6 months, at which time all 40 patients were alive without any distant metastases. Only 1 patient had local recurrence, which was discovered at 34 months follow-up. Conclusions: Non-surgical BCT can be performed with KORTUC II. KORTUC II has 3 major characteristics: it is image-guided by ultrasound, it employs enzyme-targeting, and it targets breast cancer stem cells via CD44. KORTUC II has great potential to become a valuable radiosensitizer for radioresistant neoplasms. Author Disclosure: Y. Ogawa: None. K. Kubota: None. M. Tadokoro: None. T. Yamanishi: None. N. Aoyama: None. Y. Suzuki: None. H. Iwasa: None. S. Kariya: None. M. Nogami: None. A. Nishioka: None.
2018
Early Results of a Novel Hypofractionated Schedule for Adjuvant Radiation Therapy in Early-stage Breast Cancer
C. Nelson, S. Goyal, S. Ahlawat, B. Haffty, A. Khan UMDNJ Robert Wood Johnson, New Brunswick, NJ Purpose/Objective(s): Currently reported trials of conventional whole breast irradiation (WBI) or hypofractionated (HF) WBI in patients with early stage breast cancer have shown comparable clinical and cosmetic outcomes. These trials have informed the current ASTRO guidelines for HF-WBI. Unresolved questions include the appropriateness of excluding patients with large chest wall separations, use of a breast boost in this setting, and the suitability of DCIS patients and node-positive patients. We designed a prospective phase II trial of a novel HF-WBI schedule for early stage breast cancer that incorporates a boost and limits treatment to 3 weeks. Materials/Methods: Between 2009 and 2011, 49 patients were treated at RWJUH with adjuvant breast irradiation for T1-T2 invasive breast cancer or DCIS following lumpectomy ± chemotherapy. Assuming linear-quadratic formalism and with a comparator schedule of 60 Gy in 30 fractions, we treated our study patients with WBI of 3663 Gy in 11 fractions using opposed tangents, and a boost to the tumor bed of 1332 Gy in 4 fractions using electrons or photons. Patients were not excluded from this trial based on age or chest wall separation. Treatment plans and DVH data were analyzed for dose homogeneity and patient charts were reviewed for acute and late toxicity based on common terminology criteria for adverse events. Results: The median patient age was 53 yrs (range: 39-79) with 13 patients \50 yrs. Median chest wall separation was 21.4 cm (range: 15.8-30.5) with .25 cm separation in 8 patients and median irradiated breast volume was 1414 cc (range: 430-2947). Electron boost was used in 34 patients (69%) and photon boost used in 15 (31%), with 2 patients treated in prone position and 47 supine. DVH analysis showed PTV D95 $ 95% of prescribed dose in 47/49 plans (96%). The median Dmax to the central-axis plane was 105.9% (range: 103-109%) and median Dmax to the entire irradiated breast was 105% (range: 101-108%). With median follow-up of 7.3 months (range: 1-19), acute grade 1 and grade 2 skin toxicity was reported in 59% and 37% of patients respectively and long term (.6 month) grade 1 and 2 skin toxicity was noted in 35% and 2.9% of patients, respectively. Although breast separation .25 cm was associated with higher Dmax to the whole breast (p = 0.012), this was not a significant predictors for acute toxicity (p = 0.59). Conclusions: In this trial of HF-WBI with sequential boost delivered in only 15 fractions, we have achieved ample PTV coverage while maintaining reasonable dose homogeneity for varied chest separation with no associated increase in acute skin toxicity. This novel fractionation schedule is the shortest continuous course HF-WBI schedule that is inclusive of a boost. Author Disclosure: C. Nelson: None. S. Goyal: None. S. Ahlawat: None. B. Haffty: None. A. Khan: None.
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