Tina Reis

Kypho-IORT - a novel approach of intraoperative radiotherapy during kyphoplasty for vertebral metastases

BackgroundInstable 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/Results60 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.ConclusionIn 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.

Development of a Novel Method for Intraoperative Radiotherapy During Kyphoplasty for Spinal Metastases (Kypho-IORT)

PURPOSE Approximately 30% of patients with cancer receive bone metastases, of which 50% are in the spine. Approximately 20% present with unstable lesions requiring surgical intervention, followed by fractionated radiotherapy over 2-4 weeks to prevent early regrowth. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time or hospitalization are desirable. In this study, we established a novel approach for intraoperative radiotherapy during kyphoplasty (Kypho-IORT), a method that combines stabilizing surgery and radiotherapy within one visit, after estimating the percentage of eligible patients for this treatment. METHODS AND MATERIALS To estimate the percentage of eligible patients, 53 planning CTs (897 vertebrae) of patients with spinal metastases were evaluated. The number of infiltrated vertebrae were counted and classified in groups eligible or not eligible for Kypho-IORT. The Kypho-IORT was performed in a donated body during a standard balloon kyphoplasty using the INTRABEAM system and specially designed applicators. A single dose of 10 Gy (in 10 mm) was delivered over 4 min to the vertebra. This was verified using two ionization chambers and a Monte Carlo simulation. RESULTS The estimation of eligible patients resulted in 34% of the evaluated patients, and thus 34% of patients with instable spinal metastases are suitable for Kypho-IORT. This study shows also that, using the approach presented here, it is possible to perform an IORT during kyphoplasty with an additional 15 min operation time. The measurement in the donated body resulted in a maximum dose of 3.8 Gy in the spinal cord. However, the Monte Carlo depth dose simulation in bone tissue showed 68% less dose to the prescription depth. CONCLUSION We present for the first time a system using an x-ray source that can be used for single-dose IORT during kyphoplasty. The described Kypho-IORT can decrease the overall treatment time for up to 34% of patients who usually receive radiotherapy for spinal metastases.

Intraoperative radiotherapy during kyphoplasty for vertebral metastases (Kypho-IORT): First clinical results

AIMS AND BACKGROUND Kyphoplasty is an effective procedure providing structural stability and pain alleviation in vertebral metastases. To prevent early regrowth, patients typically receive postoperative fractionated radiotherapy, which is associated with long treatment duration. Therefore, we established a new approach to deliver intraoperative radiotherapy during kyphoplasty to shorten the treatment time and reach structural stability and sterilization of the metastases (Kypho-IORT). METHODS AND STUDY DESIGN For Kypho-IORT, a 50 kV X-ray source with a specially designed applicator was used. A radiation dose of 8 Gy in 5 mm distance was delivered. After radiation the device was removed and the kyphoplasty was completed according to the standard procedure. Since August 2009, 18 patients with instable or painful spinal metastases received Kypho-IORT. The median age was 63 years (range, 43-73). RESULTS Kypho-IORT was successfully performed in 18 of 21 vertebral lesions (86%). No severe complications occurred during or early after IORT. The median pain score using a visual analogue scale decreased from 5/10 before the procedure to 2.5/10 at day 1 (P <0.001) and to 0/10 six weeks after the procedure (P = 0.001). Imaging studies were available for 15 of 18 patients. Stable disease within the irradiated vertebral body was seen in 14 patients (93%) and local progressive disease in one patient (7%). No re-irradiation due to local progressive disease or pain recurrence was necessary within the median follow-up of 4.5 months. CONCLUSIONS Kypho-IORT is well tolerated without severe side effects and provides fast improvement of pain. Although stable disease was seen in 93% of the patients, a longer follow-up is necessary to assess the effectiveness. A dose escalation study to establish the maximally tolerated dose has been initiated.

Kyphoplasty and intra-operative radiotheray, combination of kyphoplasty and intra-operative radiation for spinal metastases: technical feasibility of a novel approach

PurposeTo evaluate whether this new method is clinically applicable after theoretical and cadaver testing.MethodsThe incidence of spinal metastases requiring therapy is increasing, due to enhanced life expectancy. Due to results from studies with epidural compression a combined surgical and radiation therapy is often chosen. Minimal invasive cement augmentation is an increasingly used technique, due to fast pain relief and immediate stabilisation. On the other hand, stereotactic radiosurgery is considered to provide a more durable response and better local disease control than conventional radiotherapy with the application of higher doses. Therefore the combination of cement stabilisation and simultaneous intra-operative radiation with immediate stabilisation and high-dose radiation could be an interesting therapeutic option. The results of a clinical feasibility study are presented.Results17 patients could be treated with the new method. In two patients (10%) intra-operative radiation could not be applied. No surgical interventions for complications were required.ConclusionsSummarizing Kypho-IORT is technically feasible with an intra-operative risk profile comparable to sole kyphoplasty and a shorter treatment time and hospitalisation for the patients compared to conventional multifraction radiation. Radiation could not be applied in 10% of cases due to technical difficulties. The results of this feasibility study permit further evaluation of this new technique by a dose escalation study which is currently in preparation.

Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases

BACKGROUND CONTEXT Spinal metastases occur in 30%-50% of patients with systemic cancer. The primary goals of palliation are pain control and prevention of local recurrence. PURPOSE This study aimed to test the safety and efficacy of a combined modality approach consisting of kyphoplasty and intraoperative radiotherapy (Kypho-IORT). STUDY DESIGN/SETTING Kyphoplasty and intraoperative radiotherapy was a prospective, single-center phase I/II trial. Patients were enrolled in a classical 3+3 scheme within the initial phase I, where Kypho-IORT was applied using a needle-shaped 50 kV X-ray source at three radiation dose levels (8 Gy in 8-mm, 8 Gy in 11-mm, and 8 Gy in 13-mm depth). Thereafter, cohort expansion was performed as phase II of the trial. The trial is registered with clinicaltrials.gov, number NCT01280032. PATIENT SAMPLE Patients aged 50 years and older with a Karnofsky Performance Status of at least 60% and with one to three painful vertebral metastases confined to the vertebral body were eligible to participate. OUTCOME MEASURES The primary end point was safety as per the occurrence of dose-limiting toxicities. The secondary end points were pain reduction, local progression-free survival (L-PFS), and overall survival (OS). METHODS Pain was measured using the visual analog scale (VAS) and local control was assessed in serial computed tomography or magnetic resonance imaging scans. RESULTS None of the nine patients enrolled in the phase I showed dose-limiting toxicities at any level and thus, 52 patients were subsequently enrolled into a phase II, where Kypho-IORT was performed at various dose levels. The median pain score significantly dropped from 5 preoperatively to 2 at the first postoperative day (p<.001). Of 43 patients who reported a pre-interventional pain level of 3 or more, 30 (69.8%) reported a reduction of ≥3 points on the first postoperative day. A persistent pain reduction beyond the first postoperative day of ≥3 points was seen in 34 (79.1%) patients. The 3, 6, and 12 month L-PFS was excellent with 97.5%, 93.8%, and 93.8%. The 3, 6, and 12 months OS was 76.9%, 64.0%, and 48.4%. CONCLUSION Kyphoplasty and intraoperative radiotherapy is safe and immediately provided sustained pain relief with excellent local control rates in patients with painful vertebral metastases.

Intraoperative radiotherapy during kyphoplasty (Kypo-IORT): a novel treatment approach for patients with symptomatic spinal metastases

Palliation like pain reduction, stabilization and local control are main treatment goals for patients with spinal metastases. To shorten treatment and reduce hospitalization time, various novel therapy approaches like stereotactic body radiotherapy (SBRT) with single high-doses or minimally invasive surgical techniques (e.g., kyphoplasty) combined with other physical method are increasingly used. Intraoperative radiotherapy combined with kyphoplasty (Kypo-IORT) is an X-ray based approach using the Intrabeam ® system. It is a technically feasible therapy method with immediate pain relief and excellent local tumor control. In our recently closed dose escalation study a dose of 8 Gy in 13 mm depth from isocenter of the radiation source was determined as the maximally tolerated dose and will be tested in a phase III study.

Other Applications of INTRABEAM

Intraoperative radiotherapy (IORT) permits the delivery of a high radiation dose directly to the residual tumour or tumour bed while sparing nearby normal tissues. In most cases, IORT with the INTRABEAM® system is employed as a part of multimodal treatment, with the aim of providing an additional benefit in terms of prevention of local recurrence. IORT is used to treat many tumours, the most common being: