Elena Blank

Intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage X-rays: the first 5 years of experience with a novel approach.

PURPOSE Intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS) has been recently introduced using different devices. We report the first 5 years of a single-center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. METHODS AND MATERIALS A total of 155 breast cancers in 154 women (median age, 63 years; range, 30-83 years; T1/T2 = 100/55; N0/N+ = 108/47) were treated between February 2002 and December 2007 at the University Medical Center Mannheim, in whom IORT as tumor bed boost was applied using 50-kV X-rays (20 Gy) followed by 46-50 Gy whole-breast external-beam radiotherapy (EBRT). Chemotherapy, if indicated, was given before EBRT. The median interval between BCS plus IORT and EBRT was 40 days. Median follow-up was 34 months (maximum 80 months, 1 patient lost to follow-up). Overall survival and local relapse-free survival were calculated at 5 years using the Kaplan-Meier method. Seventy-nine patients were evaluated at 3-year follow-up for late toxicity according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic system. RESULTS Ten patients died, 2 had in-breast relapse, and 8 developed distant metastases (5-year overall survival = 87.0%; 5-year local relapse-free survival = 98.5%). Grade 3 fibroses of the tumor bed were detected in 5% of the patients after 3 years. Skin toxicity was mild (telangiectases and hyperpigmentations in approximately 6% each). CONCLUSIONS Intraoperative radiotherapy as a tumor bed boost during BCS for breast cancer using low-kilovoltage X-rays followed by EBRT yields low recurrence and toxicity rates.

Early initiation of external beam radiotherapy (EBRT) may increase the risk of long-term toxicity in patients undergoing intraoperative radiotherapy (IORT) as a boost for breast cancer

BACKGROUND Intraoperative radiotherapy (IORT) during breast-conserving surgery is increasingly used. We analyzed the influence of the interval between an IORT boost and external beam radiotherapy (EBRT) on late toxicity. METHODS Forty-eight patients received 20 Gy IORT (50 kV X-rays (Intrabeam, Carl Zeiss, Oberkochen, Germany) followed by 46-50 Gy EBRT with a median interval of 36 days (14-197). Late toxicity was assessed with the modified LENT SOMA score after a median of 36 months. RESULTS Twelve patients developed a higher grade fibrosis ( degrees II-III), three teleangiectases, one a breast edema grade degrees II, six retractions, four hyperpigmentations and five pain ( degrees II-III). The median interval between IORT and EBRT was significantly shorter in these patients (n=18) compared to the 30 patients without higher grade toxicity (29.5 days vs. 39.5 days, p=0.023, Mann-Whitney U-test). CONCLUSION Starting EBRT about 5-6 weeks after IORT appears to be associated with a decreased risk of chronic late toxicity compared with a shorter interval. The impact on local recurrence of prolonged gaps between IORT and EBRT is not known.

Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low- energy x-rays?

BackgroundRadiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy).MethodsComputer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116.ResultsIORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT.ConclusionsThe calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT.

Are Mammographic Changes in the Tumor Bed More Pronounced After Intraoperative Radiotherapy for Breast Cancer? Subgroup Analysis from a Randomized Trial (TARGIT‐A)

Intraoperative radiotherapy (IORT) with low‐energy x‐rays is increasingly used in breast‐conserving therapy (BCT). Previous non‐randomized studies have observed mammographic changes in the tumor bed to be more pronounced after IORT. The purpose of this study was to reassess the postoperative changes in a randomized single‐center subgroup of patients from a multicenter trial (TARGIT‐A). In this subgroup (n = 48) 27 patients received BCT with IORT, 21 patients had BCT with standard whole‐breast radiotherapy serving as controls. Overall 258 postoperative mammograms (median follow‐up 4.3 years, range 3–8) were retrospectively evaluated by two radiologists in consensus focusing on changes in the tumor bed. Fat necroses showed to be significantly more frequent (56% versus 24%) and larger (8.7 versus 1.6 sq cm, median) after IORT than those in controls. Scar calcifications were also significantly more frequent after IORT (63% versus 19%). The high incidence of large fat necroses in our study confirms previous study findings. However, the overall higher incidence of calcifications in the tumor bed after IORT represents a new finding, requiring further attention.

Intraoperative radiotherapy of early breast cancer using low-kilovoltage x-rays-reasons for omission of planned intraoperative irradiation.

The purpose of this study is to investigate reasons for omission of a planned intraoperative radiotherapy (IORT) during breast‐conserving surgery (BCS). Between 2002 and 2009, in 297 women an IORT during BCS was planned. In 55 women this irradiation was finally not performed. We retrospectively analyzed pre‐, peri‐, and postoperative data of these 55 women. Main reasons for omission of an IORT were insufficient tumor–skin distance (n = 20, 35.1%), an oversized wound cavity (n = 14, 24.6%), and a combination of both (n = 8, 14%). Further reasons (n = 12, 21.1%) were temporal shortage, unplanned maintenance work of the Intrabeam® device, unsuitable anatomicosurgical conditions, and ineligible histologic findings. Apart from suitable anatomic conditions, a precise preoperative ultrasonography as well as a strict interdisciplinary preoperative management is important for successful application of IORT.