Jean-Briac Prévost

Clinical accuracy of the respiratory tumor tracking system of the cyberknife: assessment by analysis of log files.

PURPOSE To quantify the clinical accuracy of the respiratory motion tracking system of the CyberKnife treatment device. METHODS AND MATERIALS Data in log files of 44 lung cancer patients treated with tumor tracking were analyzed. Errors in the correlation model, which relates the internal target motion with the external breathing motion, were quantified. The correlation model error was compared with the geometric error obtained when no respiratory tracking was used. Errors in the prediction method were calculated by subtracting the predicted position from the actual measured position after 192.5 ms (the time lag to prediction in our current system). The prediction error was also measured for a time lag of 115 ms and a new prediction method. RESULTS The mean correlation model errors were less than 0.3 mm. Standard deviations describing intrafraction variations around the whole-fraction mean error were 0.2 to 1.9 mm for cranio-caudal, 0.1 to 1.9 mm for left-right, and 0.2 to 2.5 mm for anterior-posterior directions. Without the use of respiratory tracking, these variations would have been 0.2 to 8.1 mm, 0.2 to 5.5 mm, and 0.2 to 4.4 mm. The overall mean prediction error was small (0.0 +/- 0.0 mm) for all directions. The intrafraction standard deviation ranged from 0.0 to 2.9 mm for a time delay of 192.5 ms but was halved by using the new prediction method. CONCLUSIONS Analyses of the log files of real clinical cases have shown that the geometric error caused by respiratory motion is substantially reduced by the application of respiratory motion tracking.

Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

PURPOSE To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax. RESULTS The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p=0.197). All local recurrences (n=4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade > or = 4 toxicity occurred. CONCLUSION Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.

Quality of life after stereotactic radiotherapy for stage I non-small-cell lung cancer.

PURPOSE To determine the impact of stereotactic radiotherapy on the quality of life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Overall survival, local tumor control, and toxicity were also evaluated in this prospective study. METHODS AND MATERIALS From January 2006 to February 2008, quality of life, overall survival, and local tumor control were assessed in 39 patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were treated with stereotactic radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ LC13 lung cancer-specific questionnaire were used to investigate changes in quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4, 6, 9, and 12 months after treatment, until death or progressive disease. Toxicity was evaluated using common terminology criteria for adverse events version 3.0. RESULTS Emotional functioning improved significantly after treatment. Other function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and coughing) showed no significant changes. The overall 2-year survival rate was 62%. After a median follow-up of 17 months, 1 patient had a local recurrence (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity consisted of thoracic pain, which occurred in 1 patient within 4 months of treatment, while it occurred thereafter in 2 patients. CONCLUSIONS Quality of life was maintained, and emotional functioning improved significantly after stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local tumor control was high, and toxicity was low.

Endovascular coils as lung tumour markers in real-time tumour tracking stereotactic radiotherapy: preliminary results

To evaluate the use of endovascular coils as markers for respiratory motion correction during high-dose stereotactic radiotherapy with the CyberKnife, an image-guided linear accelerator mounted on a robotic arm. Endovascular platinum embolisation coils were used to mark intrapulmonary lesions. The coils were placed in subsegmental pulmonary artery branches in close proximity to the target tumour. This procedure was attempted in 25 patients who were considered unsuitable candidates for standard transthoracic percutaneous insertion. Vascular coils (n = 87) were succesfully inserted in 23 of 25 patients. Only minor complications were observed: haemoptysis during the procedure (one patient), development of pleural pain and fever on the day of procedure (one patient), and development of small infiltrative changes distal to the vascular coil (five patients). Fifty-seven coils (66% of total inserted number) could be used as tumour markers for delivery of biologically highly effective radiation doses with automated tracking during CyberKnife radiotherapy. Endovascular markers are safe and allow high-dose radiotherapy of lung tumours with CyberKnife, also in patients who are unsuitable candidates for standard transthoracic percutaneous marker insertion.

Reducing monitor units for robotic radiosurgery by optimized use of multiple collimators

Advances in image guidance and dose delivery techniques, and increased use of hypofractionation, have led to prolonged radiotherapy fraction duration. This is also the case with robotic radiosurgery, as extensive on-line image guidance procedures, many beams, and usually high fraction doses are used for tumor irradiation. At this institution, early stage non-small-cell lung cancer patients are treated with image guided tumor tracking for respiratory motion compensation. Approximately 130 circular beams and up to approximately 39 000 monitor units (MUs) are used for delivery of a total treatment dose of 60 Gy. The large number of MUs leads to long treatment times and the radiation leakage increases with the number of MUs. Generally, per patient, a single (small) cone is used. To substantially reduce the number of MUs, the authors have developed a new planning strategy for combined use of a small and a large cone. The large cone aims at dose delivery around the PTV center, while the small cone shapes the dose around the (irregular) PTV edges. The authors systematically investigated relationships between the number of MUs, the plan quality, the selected cone diameters, and the beam-direction setup. Plan quality was assessed with the conformity index, mean lung dose (MLD), V20 of the lungs, and by visual inspection. The reduction in MUs was determined by comparing two-cone plans with corresponding one-cone plans that yielded equal MLD, i.e., equal predicted lung toxicity. With the proposed two-cone approach, the required number of MUs reduced by on average 31% (range 4%-56%). The beam-on time per treatment fraction reduced by on average 8 min (range 1-15.2 min). All plans obeyed the clinically applied constraints and were considered clinically acceptable by an involved physician.

Four-dimensional Stereotactic Radiotherapy for Early Stage Non-Small Cell Lung Cancer: A Comparative Planning Study

In this study we sought to assess the potential of the respiratory tumor tracking system of the CyberKnife to administer 3 fractions of 15 Gy in the treatment of early stage non-small cell lung cancer (NSCLC). The CyberKnife plans were compared to those developed for 3-D conformal radiotherapy (3-D CRT) administering 20 fractions of 3 Gy based on a slow CT. Ten patients with stage I NSCLC, who were previously treated with 3-D CRT, were re-planned with the CyberKnife treatment planning system. In the 3-D CRT plan, the planning target volume (PTV) included the gross tumor volume (GTV)slow and a 15-mm margin, whereas in the CyberKnife plan the margin was 8 mm. The physical doses from both treatment plans were converted to normalized total doses (NTD) using the linear quadratic model with an α/βtumor of 10 Gy and α/βorgans at risk (OAR) of 3 Gy. The average minimal and mean doses administered to the PTV with the CyberKnife and 3-D CRT were 93 and 115.8 Gy and 61 and 66 Gy, respectively (p<0.0001). The mean V20 of the CyberKnife and 3-D CRT plans were 8.2% and 6.8%, respectively (p=0.124). Both plans complied with the OAR constraints. In conclusion, 4-dimensional stereotactic radiotherapy can increase the minimal and mean biological dose with 51% and 75%, in comparison with 3-D CRT without significantly increasing the V20, respectively.

Analysis of the motion of oropharyngeal tumors and consequences in planning target volume determination.

PURPOSE To determine adequate three-dimensional (3D) margins around the clinical target volume (CTV) of oropharyngeal cancers. METHODS AND MATERIALS The CTV, bounded by implanted markers, was recorded under fluoroscopy in antero-posterior (AP) and lateral view. The peak-to-peak motion was measured in lateral, AP and cranio-caudal (CC) directions. RESULTS During swallowing, the mean amplitude of motion measured was 9.4mm (0.9-18.5) and 4.1mm (0.6-11.4) in AP view in the CC and lateral direction, respectively; and 8.6mm (0.5-16.5) and 7.6mm (0.9-14.5) in lateral view in the CC and AP direction, respectively. In the non-swallowing period the motion was 1.5mm (0.3-3.2) and 1mm (0.4-3.6) in AP view in the CC and lateral direction, respectively; and 1.3mm (0.4-3.1) and 1.3mm (0.4-3.4) in lateral view in the CC and AP direction, respectively. This motion was believed to be due to breathing. CONCLUSION If swallowing can be suppressed during CT acquisition, the contribution to the internal margin for this motion is negligible. Breathing related motion is also believed to be of limited clinical relevance in current practice. However, it might become of importance in future, with further reduction of margins.

Robotic Radiosurgery vs. Brachytherapy as a Boost to Intensity Modulated Radiotherapy for Tonsillar Fossa and Soft Palate Tumors: The Clinical and Economic Impact of an Emerging Technology

As a basis for making decisions regarding optimal treatment for patients with tonsillar fossa and soft palate tumors, we conducted a preliminary investigation of costs and quality of life (QoL) for two modalities [brachytherapy (BT) and robotic radiosurgery] used to boost radiation to the primary tumors following external beam radiotherapy. BT was well established in our center; a boost by robotic radiosurgery was begun more recently in patients for whom BT was not technically feasible. Robotic radiosurgery boost treatment has the advantage of being non-invasive and is able to reach tumors in cases where there is deep parapharyngeal tumor extension. A neck dissection was performed for patients with nodal-positive disease. Quality of life (pain and difficulty swallowing) was established in long-term follow-up for patients undergoing BT and over a one-year follow-up in robotic radiosurgery patients. Total hospital costs for both groups were computed. Our results show that efficacy and quality of life at one year are comparable for BT and robotic radiosurgery. Total cost for robotic radiosurgery was found to be less than BT primarily due to the elimination of hospital admission and operating room expenses. Confirmation of robotic radiosurgery treatment efficacy and reduced morbidity in the long term requires further study. Quality of life and cost analyses are critical to Health Technology Assessments (HTA). The present study shows how a preliminary HTA of a new medical technology such as robotic radiosurgery with its typical hypofractionation characteristics might be based on short-term clinical outcomes and assumptions of equivalence.

Dose Escalation with the Frameless Respiratory Tumor Tracking System of the CyberKnife for Early Stage Non-Small-Cell Lung Cancer

We used the respiratory movement tracking system of the CyberKnife®, called Synchrony® (Accuray Incorporated, Sunnyvale, CA), to develop dose plans delivering 45 Gy (3 times 15 Gy) for the treatment of early stage non-small cell lung cancer (NSCLC). Characteristics of those plans were compared with plans developed for 3-Dimensional conformal radiotherapy (3D-CRT) administering 60 Gy (20 times 3 Gy) based on a slow CT. Ten patients with Stage I NSCLC previously treated with 3DCRT were replanned with the CyberKnife treatment planning system. In the 3D-CRT plan, the planning target volume (PTV) equaled the gross tumor volume (GTV)slow + 15 mm. In the CyberKnife plan, the PTV equaled the GTV + 8 mm. The physical dose of both treatment plans was converted into the normalized total dose using the linear quadratic model with an α/βtumor = 10 Gy and α/βorgans at risk(OAR) = 3 Gy. The mean doses administered to the PTV with the CyberKnife and 3D-CRT were 115.8 Gy and 66 Gy, respectively (p < 0.0001). The mean V20 of the CyberKnife and 3D-CRT plan was 8.2% and 6.8%, respectively (p=0.124). Both plans respected the constraints of the other organs at risk (OAR). In this context the CyberKnife can administer a much higher biological dose than 3D-CRT without increasing the dose (V20) to the lungs.

P3-045: Lung tumor tracking during 4-dimensional stereotactic radiotherapy treatment with the cyberknife: early results

Protons and C-ions for the treatment of non-small cell lung cancer (NSCLC): What is published the evidence? Pijls-Johannesma, Madelon Lambin, Philippe De Ruysscher, Dirk MAASTRO Clinic, GROW, University Hospital Maastricht, Maastricht, The Netherlands Background: The prognosis of patients with NSCLC is still poor. Amongst distant metastases, also local tumour recurrence is still a problem. Because charged particles (protons and C-ions) have a better dose-distribution than the currently used photons, at least from a theoretical point of view, they should lead to superior results compared to photons. On top of the physical superiority of protons over photons, C-ions also display a biological advantage. Aim: In this review, we searched for clinical evidence that protons or C-ions would really be beneficial to patients with NSCLC. Methods: We performed a review based on published literature by means of a standardized query using the following electronic databases (up until January 31, 2007): CINAHL, EMBASE and MEDLINE. There was no limit applied to publication year, language or study design. Search terms (using free text words as well as MESH terms) were used alone or in combination, related to lung cancer and charged particle treatment. This included the following terms: neoplasm, cancer, carcinoma, lung cancer, proton, ion, charged particle and hadron. Results: Six fully published series (protons:3, C-ions:3), all dealing with NSCLC, mainly stage I, were identified. No phase III trials could be identified. On proton therapy, weighted means of 2-5 year local tumour control rates varied between 68% and 84%. The weighted mean for 2 year/5 year overall survival and 2 year/5 year cause specific survival were 53%/23% and 66%/46% respectively. Radiation induced pneumonitis was observed in about 10% of the patients. On C-ion therapy, the local tumour control rate was 77% and the 5 year overall survival and cause specific survival rates were 42% and 60% respectively. Conclusion: The results with charged particles, at least for stage I disease, seem to be better than that which is generally achieved by conventional radiotherapy. However, they seem to be similar to what may be achieved with hypofractionated “stereotactic” photon techniques, with which in several phase I/II studies, local tumour control rates of 90 % and more were reported. Due to the overwhelming theoretical data on the beneficial properties of protons and light ions, further investment in the infrastructure needed to perform large trials in patients with different lung cancer stages, is warranted. Until these results are available, for lung cancer, charged particle therapy should be considered as experimental.