EP-1215: Introducing new radiation oncology technology through small scale clinical trial methodology

S60 Purpose/Objective: To analyze the acute, late toxicity and esthetic outcome in early breast cancer patients treated with hypofractionated radiotherapy (H-RT) preceded by IORT or followed by sequential boost (SB). Materials and Methods: 129 women with invasive breast cancer stages I and II received H-RT, 42.40 Gy (2.65Gy x 16 #) preceded by IORT (10 Gy in single fraction) in 53 patients (IORT/H-RT) or followed by SB (10 Gy2.50 Gy x 4 #) in 76 patients (H-RT/SB). RTOG/EORTC toxicity scales were used to score acute and late skin toxicity and ultrasound analysis to assign a value to skin thickening. Cosmetic outcome was assessed comparing treated with untreated breast. Results: Acute skin toxicity of Grade 1, 2 or 3 was experienced by 58.5%, 3.7% and 0% of IORT/H-RT versus 67.1%, 9.2% and 1.3% of H-RT/SB patients. After an average of 26.5 months, late skin toxicity of Grade 1 or 2 was experienced by 34% and 1.8% of IORT/H-RT versus 42.2% and 7.8% H-RT/SBpatients. Skin thickening was greater in H-RT/SB (35.3%) than in IORT/H-RT group (8.1%). Long term cosmetic outcome was excellent or good in 94.3% of IORT/H-RT and in 72.3% of H-RT/SB patients. Results were statistically significant(p<0.001). Conclusions: Respect to SB, IORT reduces the acute and late skin toxicity, improving the subjective perception of the cosmetic outcome in early breast cancer patients treated with H-RT. EP-1213 Unintended irradiation of internal mammary chain - is that enough? M. Silva1, L.G. Sapienza1, M.J. Chen1, D.G. Castro1, A.C.A. Pellizzon1, M.A.C. Maia1 1 AC Camargo Cancer Center, Radiation Oncology, São Paulo - São Paulo, Brazil Purpose/Objective: To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed. Materials and Methods: We analyzed 112 consecutive conformal radiotherapy plans, correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques. For statistical analysis, we used the Mann-Whitney-Wilcoxon test (R software). Results: The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy and 18.67 Gy, respectively. It was detected significant differences between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). The inclusion of an additional field to the supraclavicular fossa region did not influence the IMC coverage (p = 0.57). Mean doses to IMC where greater in patients with more advanced tumor stage (T3-T4) when compared with more initial stages (
ESTRO 33, 2014 reconstruction, irrespective of when RT is given in relation to surgery. Late tissue side effects RT-induced are capsular contracture, impaired skin healing, implant rupture, malpositioning or extrusion. However, not all reports indicate poor aesthetic outcome and satisfaction in women undergoing immediate reconstruction and RT. When adjuvant RT is indicated, delayed reconstruction is preferred. But some times it’s impossible, because the indication for postoperative RT arises after surgery, or by patient’s explicit request. Here we present our experience in treating patients after breast reconstruction with a breast expander and further replacement by a definitive silicone implant. Materials and Methods: We evaluated 32 patients treated in our department. All of them were treated with full expander, started RT after the last expansion and received 50Gy/25fr. Aesthetic evaluation was performed at least six months after the expander substitution by a definitive implant, and was carried out by two independent physicians. Patients answered a QOL and satisfaction questionnaire. If necessary, patients received local massages for early intervention on fibrosis. Dosimetric disturbances produced by the expander membrane were studied. Results: All patients experienced some grade of fibrosis (minimized with local massages performed by the Aesthetic Surgery Department), although none developed infection, dehiscence or necrosis. No differences in acute toxicity compared to conventional treatment, nor dosimetric disturbances higher than 5% were found. For physicians and patients, aesthetic outcome was acceptable, good or excellent in 90% of the patients evaluated. Furthermore, all patients considered this approach as very positive in terms of self esteem and global satisfaction. Conclusions: Regarding the good results achieved in aesthetic and satisfaction, although preferred treatment choice in this patients is delayed reconstruction, if a patient with an expander has to be treated RT can be delivered with the expander completely full. EP-1215 Introducing new radiation oncology technology through small scale clinical trial methodology B. Chua1, M. Bressal2, D. Phillips3, A. Phillips3, S. David1, T. Kron4, P. Tran1 1 Peter Mac Callum Cancer Centre, Radiation Oncology, Melbourne, Australia 2 Peter Mac Callum Cancer Centre, Biostatistics, Melbourne, Australia 3 Peter Mac Callum Cancer Centre, RTT, Melbourne, Australia 4 Peter Mac Callum Cancer Centre, Physics, Melbourne, Australia Purpose/Objective: To develop a safe and effective method for introducing new radiation oncology technologies and techniques (NROTAT) into a clinic using a small scale clinical trial. The process should provide an estimate of a) the proportion of patients whomay benefit from the NROTAT b) the magnitude of benefit the NROTAT could provide over conventional treatment, and c) the feasibility of the NROTAT in routine care Materials and Methods: Figure 1 shows the clinical trial schema. It was tested in the setting of introducing deep inhalation breath hold(DIBH) for the reduction of heart dose in patients undergoing adjuvantradiotherapy for left breast cancer. The trial was approved by theinstitutional ethics review board to recruit 10 patients for treatment with DIBHguided radiotherapy. Eligibility criteria, the mean heart dose from aconventional (non-DIBH guided) treatment plan that would warrant the use of DIBH,and the minimum benefit to be achieved using DIBH to warrant its application weredefined a-priori. Eligibility criteriaincluded patients who were to have radiotherapy for left breast cancer, were aged>50 years due to the potential small risk of radiation related malignancyarising from the two CT scans required for conventional and DIBH planning. To warrantapplication of the new technique the mean heart dose had to be >2 Gy in theconventional plan. The trial would also stop if >16 consecutive patients whomet the criteria for DIBH could not complete treatment due to patient ortreatment related reasons. Figure 1: Schema of the small scale clinical trial used tointroduce new radiation oncology technologies and techniques.

ESTRO 33, 2014

S61 EP-1217 Acelerated Partial Breast Irradiation (APBI) with high dose rate brachytherapy in luminal breast cancer B. Pinar1, J. Blanco1, A. Riveros-Pérez1, L. García-Cabrera1, M.A. Cabezón-Pons1, N. Rodríguez-Ibarria1, L.A. Henríquez-Hernández1, M. Federico1, M. Lloret1, P.C. Lara1 1 Hospital Universitario de Gran Canaria Dr. Negrín, Radiation Oncology, Las Palmas de Gran Canaria, Spain Purpose/Objective: Most recurrences after breast conserving surgery occur within the index quadrant. Partial breast irradiation might be then adequate for selected patients. High dose rate brachytherapy (HDR-BT) is a feasible and comfortable technique for this partial approach. The aim of the study was to evaluate the role of APBI with HDR-BT in molecular subtype luminal cases and evaluate de ASTRO elegibility criteria for such treatment.

Figure 1: Schema of the small scale clinical trial used tointroduce new radiation oncology technologies and techniques. Results: Ten of 12 eligible patients had amean heart dose > 2Gy in the conventional plan and thus had a second CT scanand treatment plan using DIBH. All 10 patients had a reduction of mean heartdose by more than 30% and proceeded to treatment delivery using DIBH. Allpatients were able to hold their breath for >12 seconds to enable DIBHguided radiotherapy. Nine patients benefited from optical feedback during DIBH.Daily electronic portal images confirmed that the treatment was delivered asplanned. Conclusions: Using implementation of DIBH for patientsundergoing radiotherapy for left breast cancer as an example, we demonstratedthe utilisation of clinical trials methodology for the safe and effective introductionof NROTAT. Patient eligibility, the new technology or technique, and thecriteria for its application must be clearly defined prospectively to enable anassessment of the proportion of patients who may benefit from the NROTAT andthe magnitude of improvement over conventional treatment. These data informsthe decision on whether and how the NROTAT should be implemented in routinecare. EP-1216 Hypofractionated RT for breast cancer ñ acceleration of the START A regime: Intermediate tolerance and efficacy S. Janssen1, C. Glanzmann1, S. Lang1, S. Verlaan1, D. Wisler1, C. Linsenmeier2, G. Studer2 1 University Hospital Zurich, Radiooncology, Zurich, Switzerland 2 Triemli Hospital, Radiooncology, Zurich, Switzerland Purpose/Objective: Prospective evaluation of accelerated hypofractionated radiotherapy (RT) in breast cancer patients treated with 41.6 Gy in 13 fractions plus boost delivered five times a week. Materials and Methods: Between 03/2009 and 10/2012 98 consecutive patients aged >55years presenting with breast cancer (invasive cancer: n=95, ductal carcinoma in situ (DCIS): n=3) after breast conserving surgery were treated in our institution using the following schedule: 41.6 Gy in 13 fractions 4 times a week and 9 or 12 Gy boost with electrons in 3 or 4 fractions (on day 5 each week), cumulative dose: 50.6 Gy in 3.2 weeks or 53.6 Gy in 3.4 weeks, respectively depending on resection status. 56 patients had a T1 tumor, 39 a T2 tumor. N-situation was as follows: N0: n=71, N1: n=25, N2/3: n=2. 23 patients (24%) received chemotherapy before RT. A prospectively planned FU visit with objective and subjective assessment of treatment tolerance (questionnaires) was performed 0 and 8 weeks after RT completion, and 1, 2 and 4 years later, respectively. Results: Mean/median follow-up time was 32/28 months (range: 12-56). After 3 years local control, loco-regional control and disease-free survival was 100%, 100%, and 98%, respectively. Overall survival was 96%. Cosmetic outcome was very good with patients being satisfied or very satisfied in 99% (n=86/87), 97% (n=55/57) and 100% (n=25/25) after one, two and four years after RT, respectively. No grade 2 pain or more was described after 4 years. Fibrosis, telangiectasia and edema are comparable to other trials. Conclusions: The presented hypofractionated RT regime with single doses of 3.2 Gy plus boost doses of 3-4x 3Gy applied in 5 sessions a week seems well tolerated on intermediate term FU. A correlation of toxicity and planning target volumina and dose statistics will be presented.

Materials and Methods: Between 2007 and 2013, 132 patients with early stage breast cancer after conservative surgery were treated and prospectively followed in our institution with HDR-BT adapted to surgical bed, and CT-based 3D dosimetry, delivering a dose of 32 Gy in 8 fractions of 4 Gy, as the unique adjuvant radiation treatment. The mean age at treatment was 67years (range 45-92). Patients were included as molecular low risk cases: ER positive (93.7%), PR positive (85.6%) Her-2 negative (86.4%), p53 negative(90%). 82% were infiltrating ductal carcinomas, tumour stage was 0/I in 93.2% of cases and 109 (93.3%) patients were classified as luminal molecular subtypes. ASTRO classification was elegible in 83 patients (68,6%) and cautionary in 35 (28,9%). Seventy three patients received adjuvant hormonal therapy. Results: With a mean follow-up of 23.5 months (range 2-60), only one patient had local recurrence in the ipsilateral breast 25 months after the procedure. Actuarial Local Disease Free Survival at 4 years was 96%. Five patients died during follow-up, one from distant relapse from the breast cancer and 4 from other causes. Late toxicity (CTCAE 4.0) was mild, with 24% and 3.3% of grade I or II cutaneous toxicity and 9.9% and 0.8% subcutaneous grade I or II toxicity. No toxicity grade III was found. Conclusions: HDR-BT APBI is a safe treatment for luminal molecular subtype breast cancer, with excellent results in terms of normal tissue late toxicity. ASTRO classification suitable vs. cautionary showed no differences in outcomes. EP-1218 Moisturizer efficacy for breast radiation-induced dermatitis: A prospective open-label, randomized trial M. Ogita1, K. Sekiguchi1, K. Akahane2, C. Haga1, R. Ito1, Y. Ishida3, S. Arai4, J. Kawamori1 1 St. Luke's International Hospital, Radiation Oncology, Tokyo, Japan 2 Saitama Medical Center Jichi Medical University, Radiology, Saitama, Japan 3 Ehime Prefectual Central Hospital, Pediatrics, Matsuyama, Japan 4 St. Luke's International Hospital, Dermatology, Tokyo, Japan Purpose/Objective: Breast irradiation is known to cause the destruction of sebaceous and sweat glands, which, in turn, decreases skin water content and affects patient QOL. We aimed to assess whether use of a moisturizer decreases the severity of radiation-induced breast skin dryness. Materials and Methods: From April 2011 to June 2013, 65 breast cancer patients who received adjuvant radiotherapy (RT) after lumpectomy were randomly assigned to two groups; A) use of the heparinoid moisturizer (Hirudoid®) twice daily starting 2 weeks after the completion of whole breast RT (WBRT); and B) no treatment. RT included tangential fields to the whole breast (± supraclavicular region, 48-50Gy) with or without an electron boost to the tumor bed (10-18Gy). The water content of the irradiated breast skin was measured with corneometer at the beginning of RT, on the last day of WBRT, and at two weeks, four weeks and three months after WBRT; the skin water content ratio (irradiated skin water content divided by contralateral breast water content) was calculated. The primary endpoint was the difference in corneometer-measured skin water content ratio four weeks after WBRT compared with at two weeks after WBRT. Pain and pruritus scores were observed using the Visual Analog Scale (VAS) at each point. The skin water content ratio was analyzed by Wilcoxon signed-rank test with Bonferroni correction. Differences in skin water content ratio and VAS scores were analyzed by the Mann-Whitney U test. This study is registered, UMIN-CTR5532. Results: Three patients were excluded because of protocol violation. A total of 62 patients were analyzed. The average age of patients were 47.8 (range 32-65) and 51.1 (39-65) in the moisturizer group and no