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.

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 during breast-conserving surgery using a miniature x-ray generator (Intrabeam®): theoretical and experimental background and clinical experience.

Breast cancer is currently the most frequent indication for intraoperative radiotherapy with increasing numbers worldwide. Intraoperative radiotherapy can be used as a tumor bed boost followed by whole breast radiotherapy, or as a distinct form of accelerated partial breast irradiation in selected patients. This article summarizes the theoretical background including pattern of recurrence and distribution of tumor cell foci in the breast and discusses the rationale for intraoperative radiotherapy, especially using a miniature x-ray generator (Intrabeam(®)). The concepts of how to avoid geographic and temporal miss by giving radiotherapy during surgery to the open wound cavity are described. Experimental and clinical experience is presented based on in vitro experiments and more than 300 treated patients in a single department with mature follow-up.

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

BACKGROUND: Radiation 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). METHODS: Computer-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. RESULTS: IORT 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. CONCLUSIONS: The 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.

Single-center long-term follow-up after intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage x-rays.

BACKGROUND: Intraoperative radiotherapy (IORT) during breast-conserving surgery as a boost followed by whole-breast radiotherapy is increasingly used. METHODS: Between February 2002 and December 2008, a total of 197 patients were treated with IORT as a boost (20 Gy, 50 kV x-rays; Intrabeam System, Carl Zeiss Surgical, Oberkochen, Germany) during breast-conserving surgery, followed by whole-breast radiotherapy (46-50 Gy). Systemic therapy was provided according to the St. Gallen consensus. Patients were recalled every 6-12 months for follow-up. Findings were scored according to the LENT-SOMA scale. RESULTS: Median age was 61.8 (range 30-84) years, and median follow-up was 37 (range 5-91) months. There were T1, T2, and Tx tumors in 129, 67, and 1 patients, respectively, and N0, N1, N2, and N3 disease in 144, 36, 15, and 2 patients, respectively. Until December 2009, 5 local invasive relapses, 1 local ductal carcinoma-in-situ, 1 axillary relapse, 6 secondary cancers, and 11 distant metastases were seen, resulting in a 5-year disease-free survival of 81.0% and an overall survival of 91.3%. Local relapse-free survival (invasive cancers) at 3 and 5 years was 97.0%. After a follow-up of 5 years (n =58), only 8 patients (13.8%) had chronic skin toxicities, and 2 patients (3.4%) had a marked increase in density (fibrosis III), while 62.0% had no/barely palpable fibrosis 0-I. Other toxicities observed included severe pain (n = 4, 6.9%), retraction (n =17, 29.3%), edema of the breast (n =1, 1.7%), and lymphedema in general (n =2, 3.4%). CONCLUSIONS: After IORT as a tumor bed boost with low-kilovoltage x-rays followed by whole-breast radiotherapy, low local recurrence and chronic toxicity rates were seen after 5-year follow-up.

Health-related quality of life after breast-conserving surgery and intraoperative radiotherapy for breast cancer using low-kilovoltage X-rays.

BACKGROUND: Intraoperative radiotherapy (IORT) is currently being evaluated as a novel approach during breast-conserving surgery (BCS). IORT can be used either as a tumor bed boost followed by external-beam radiotherapy (EBRT) or as a single treatment. In a matched-pair study, we assessed quality of life (QoL) in 69 patients with early breast cancer treated with BCS and/or IORT and/or EBRT. METHODS: Patients were matched for age and time since BCS. IORT was provided with 50 kV x-rays (Intrabeam) delivering 20 Gy at the applicator surface. EBRT (46 to 50 Gy in 2-Gy fractions in the IORT with EBRT group, and 56 Gy in 2-Gy fractions in the EBRT group) was initiated after completion of wound healing and/or chemotherapy. The mailed questionnaires included the European Organization for the Research and Treatment of Cancer QLQ-C30 and BR23, FACT-F, HADS, Body Image Scale, and Rosenberg Self-Esteem Scale. At 18 to 70 months' follow-up (median 47 months), all patients were disease free. RESULTS: We found only a few differences between the three groups. There was a trend toward more pain (mean ± standard deviation; 42.8 ± 32.9 vs. 27.5 ± 34.7) and reduced QoL (57.6 ± 20.7 vs. 70.3 ± 23.9) after IORT with EBRT compared with EBRT, respectively. IORT patients reported comparable QoL (70.3 ± 23.0), and less breast symptoms and body image concerns compared to EBRT (8.6 ± 12.3 vs. 19.2 ± 23.8, and 1.7 ± 3.3 vs. 3.4 ± 4.4, respectively). IORT alone resulted in significantly fewer breast symptoms (8.6 ± 12.3; P = 0.012) and less pain (23.9 ± 24.5, P = 0.041) compared with IORT with EBRT (26.1 ± 27.6; 42.8 ± 32.9, respectively). CONCLUSIONS: Patients with early breast cancer after BCS and IORT with or without EBRT present with comparable QoL like patients receiving EBRT without a boost. IORT patients show the lowest rate of breast symptoms.

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.