Search

Accelerated partial breast irradiation (APBI) has been under clinical investigation for more than 15 years. There are several technical approaches that are clinically established, e.g. brachytherapy, intraoperative radiotherapy (IORT), or external-beam radiotherapy. The understanding of the underlying biology, optimal technical procedures, patient selection criteria, and imaging changes during follow-up has increased enormously. After completion of several phase III trials using brachytherapy or IORT, APBI is currently increasingly used either in phase IV studies, registries, or in selected patients outside of clinical studies. Consensus statements about suitable patients are available from several international and national societies like ASTRO, ESTRO, and DEGRO. One may expect that 15-25% of patients undergoing breast-conserving surgery may qualify for APBI, i.e. patients with small invasive ductal breast cancer without clinical lymph node involvement.

According to their carcinogenesis, colorectal cancer (CRC) subtypes show distinct molecular parameters. Hereditary non-polypous colorectal cancer (HNPCC) is the most common inherited CRC characterized by clinical criteria and confirmed microsatellite instability (MSI). Interestingly, a recently identified subtype, familial colorectal cancer type X (FCC-X), shows the same clinical criteria but microsatellite stability (MSS). CEACAM1 is a known tumor suppressor that regulates apoptosis in colon cells, and its loss is one of the most frequent events in early tumorigenesis of CRC. Therefore its loss may characterize precursor colon cells prior to neoplastic transformation. We analyzed tumor specimens of HNPCC and FCC-X patients in order to investigate whether there is a loss of CEACAM1 expression analogous to sporadic CRC and whether the expression of CEACAM1 would distinguish between these tumor entities. No differences in CEACAM1 expression were noted between HNPPC (n = 38) and FCC-X (n = 30) tumors. CEACAM1 was reduced in near-identical frequencies in 36/38 (95%) HNPCC and 29/30 (97%) FCC-X. This is the first report to demonstrate the loss of CEACAM1 expression in hereditary CRC. There was no difference between HNPCC and FCC-X. The frequency of expression loss was comparable to sporadic CRC, indicating that loss of CEACAM1 is an early event in colorectal tumorigenesis linking the genesis of sporadic and hereditary CRC.

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.

Background Instable and painful vertebral metastases in patients with progressive visceral metastases present a common therapeutic dilemma. We developed a novel approach to deliver intraoperative radiotherapy (IORT) during kyphoplasty and report the first treated case. Methods/Results 60 year old patient with metastasizing breast cancer under chemotherapy presented with a newly diagnosed painful metastasis in the 12th thoracic vertebra. Under general anaesthesia, a bipedicular approach into the vertebra was chosen with insertion of specially designed metallic sleeves to guide the electron drift tube of the miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany). This was inserted with a novel sheet designed for this approach protecting the drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated after IORT and polymethylmethacrylate cement was injected. The whole procedure lasted less than 90 minutes. Conclusion In conclusion, this novel, minimally invasive procedure can be performed in standard operating rooms and may become a valuable option for patients with vertebral metastases providing immediate stability and local control. A phase I/II study is under way to establish the optimal dose prescription.

Background Patients ≥ 70 years with small, low-risk breast cancer who are operated but not irradiated how local relapse rates around 4% after 4 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to 1% after 4 years under Tamoxifen. It has been demonstrated that the efficacy of radiotherapy of the tumor bed only in a selected group can be non-inferior to WBRT. Methods/Design This prospective, multicentric single arm phase II study is based on the protocol of the international TARGIT-A study. The TARGIT-E study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of elderly patients with small breast cancer and absence of risk factors. Patients will receive IORT (20 Gy with Intrabeam system/Carl Zeiss) during breast conserving surgery. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines. Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral in breast relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome. The expected local relapse rates are 0.5/1/1.5% after 2.5/5/7.5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Power calculations result in 540 patients with a calculated dropout rate of 20% and loss to follow-up of 20%, an alpha of 0.01 and a beta 0.05. There will be a pre- and a post-pathology stratum (n = 270 each). Discussion It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam system (Carl Zeiss) can recruit patients into the trial. Its aim is to confirm the efficacy and toxicity of IORT in a well selected collective of elderly patients with breast cancer. Trail registration NCT01299987