Factors affecting the accuracy of respiratory tracking of the image-guided robotic radiosurgery system.

PURPOSE: To analyze the factors affecting the tracking accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS). MATERIALS AND METHODS: A dynamic motion phantom (motion phantom) reproduced the respiratory motions of each patient treated with the SRTS using a ball as the target. CyberKnife tracked the ball using the SRTS, and this process was recorded by a video camera mounted on the linear accelerator head. The tracking error was evaluated from the images captured by the video camera. Multiple regression analysis was used to identify factors affecting tracking accuracy from 91 cases. RESULTS: The median tracking error was 1.9 mm (range 0.9-5.3 mm). Four factors affected the tracking accuracy: the average absolute amplitude of the tumor motion in the cranio-caudal (CC) direction (p = 0.007), average position gap due to the phase shift between the internal tumor and external marker positions in the CC direction (p < 0.001), and average velocity of the tumor in the CC (p < 0.001) and anterior-posterior directions (p = 0.033). CONCLUSION: We identified factors that affected tracking accuracy. This information may assist the identification of suitable margins that should be added to each patient's clinical target volume.

CyberKnife Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy As First-line Treatments for Imaging-diagnosed Intracranial Meningiomas.

Definitive radiotherapy is an important alternative treatment for meningioma patients who are inoperable or refuse surgery. We evaluated the efficacy and toxicity of CyberKnife-based stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hSRT) as first-line treatments for intracranial meningiomas that were diagnosed using magnetic resonance imaging (MRI) and/or computed tomography (CT). Between February 2005 and September 2015, 41 patients with intracranial meningiomas were treated with CyberKnife-based SRS or hSRT. Eleven of those tumors were located in the skull base. The median tumor volume was 10.4 ml (range, 1.4-56.9 ml). The median prescribed radiation dose was 17 Gy (range, 13-20 Gy to the 61-88% isodose line) for SRS (n = 9) and 25 Gy (range, 14-38 Gy to the 44-83% isodose line) for hSRT (n = 32). The hSRT doses were delivered in 2 to 10 daily fractions. The median follow-up period was 49 months (range, 7-138). The 5-year progression-free survival rate (PFS) for all 41 patients was 86%. The 3-year PFS was 69% for the 14 patients with tumor volumes of ≥13.5 ml (30 mm in diameter) and 100% for the 27 patients with tumor volumes of <13.5 ml (P = 0.031). Grade >2 toxicities were observed in 5 patients (all of them had tumor volumes of ≥13.5 ml). SRS and hSRT are safe and effective against relatively small (<13.5 ml) meningiomas.

A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

BACKGROUND: In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. METHODS: Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. RESULTS: Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. CONCLUSION: The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

Comparison of multileaf collimator and conventional circular collimator systems in Cyberknife stereotactic radiotherapy.

Multileaf collimator (MLC) technology has been newly introduced with the Cyberknife system. This study investigated the advantages of this system compared with the conventional circular collimator (CC) system. Dosimetric comparisons of MLC and CC plans were carried out. First, to investigate suitable target sizes for the MLC mode, MLC and CC plans were generated using computed tomography (CT) images from 5 patients for 1, 3, 5 and 7 cm diameter targets. Second, MLC and CC plans were compared in 10 patients, each with liver and prostate targets. For brain targets, doses to the brain could be spared in MLC plans better than in CC plans (P ≤ 0.02). The MLC mode also achieved more uniform dose delivery to the targets. The conformity index in MLC plans was stable, irrespective of the target size (P = 0.5). For patients with liver tumors, the MLC mode achieved higher target coverage than the CC mode (P = 0.04). For prostate tumors, doses to the rectum and the conformity index were lowered in MLC plans compared with in CC plans (P ≤ 0.04). In all target plans, treatment times in MLC plans were shorter than those in CC plans (P < 0.001). The newly introduced MLC technology can reduce treatment time and provide favorable or comparable dose distribution for 1-7 cm targets. In particular, the MLC mode has dosimetric advantage for targets near organs at risk. Therefore, the MLC mode is recommended as the first option in stereotactic body radiotherapy.

Hypofractionated Stereotactic Radiotherapy for Auditory Canal or Middle Ear Cancer.

BACKGROUND: Stereotactic radiotherapy (SRT) may represent a new treatment option for individuals with auditory canal or middle ear cancer. METHODS: Study participants with pathologically proven ear cancer were treated with SRT (35 Gy for 3 fractions or 40 Gy for 5 fractions) as first-line therapy. When local tumor recurrence developed following SRT, subtotal temporal bone resection and postoperative chemoradiotherapy were performed as salvage treatment. Boluses were used for the initial 14 study patients. RESULTS: Twenty-nine study participants were enrolled and staged with T1 (n = 3), T2 (n = 7), T3 (n = 14), or T4 disease (n = 5). Three-year overall survival rates were 69% for T1/2 disease, 79% for T3 disease, and 0% for T4 disease. Three-year local control rates were 70% for T1/2 disease, 50% for T3 disease, and 20% for T4 disease. Grade 2 or higher dermatitis or soft-tissue necrosis occurred more frequently in study patients treated with boluses (8/14 vs 2/15; P = .02). Salvage treatment was safely performed for 12 recurrent cases. CONCLUSIONS: These results suggest that SRT outcomes are promising for patients with ear cancer (? T3 disease). The rate of toxicity was acceptable in the study patients treated without boluses. Outcomes of salvage surgery and postoperative radiotherapy following SRT were also encouraging.

Re-irradiation of recurrent anaplastic ependymoma using radiosurgery or fractionated stereotactic radiotherapy.

PURPOSE: Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed. METHODS: Eight patients with recurrent ependymomas fulfilling the criteria described below were evaluated. Inclusion criteria were: (1) the patient had previously undergone surgery and conventional radiotherapy as first-line treatment; (2) targets were located in or adjacent to the eloquent area or were deep-seated; and (3) the previously irradiated volume overlapped the target lesion. RESULTS: FSRT was delivered to 18 lesions, SRS to 20 lesions. A median follow-up period was 23 months. The local control rate was 76 % at 3 years. No significant differences in local control were observed due to tumor size or fractionation schedule. Lesions receiving >25 Gy/5 fr or 21 Gy/3 fr did not recur within 1 year, whereas no dose-response relationship was observed in those treated with SRS. No grade ≥2 toxicity was observed. CONCLUSION: Our treatment protocol provided an acceptable LC rate and minimal toxicities. Because local recurrence of tumors may result in patient death, a minimum dose of 21 Gy/3 fr or 25 Gy/5 fr or higher may be most suitable for treatment of these cases.

Partial-brain radiotherapy for primary central nervous system lymphoma: multi-institutional experience.

Whole-brain radiotherapy (WBRT) has been an important component of treatment for primary central nervous system lymphoma (PCNSL), but delayed neurotoxicity has been a matter of concern. We have employed partial-brain radiotherapy (PBRT) with wide margins for PCNSL patients with a single lesion or a few lesions. In this study, we evaluated the treatment outcome in PCNSL patients undergoing PBRT. Between 2003 and 2014, 24 patients were treated with PBRT; 16 received high-dose-methotrexate (MTX) -containing chemotherapy before PBRT. Conventional fractionation with a median dose of 54 Gy was used. For reference, 15 patients undergoing MTX-based chemotherapy and WBRT were also analyzed. The 3-year overall survival rate was 60% for all 24 patients undergoing PBRT and 68% for the 16 patients undergoing MTX-based chemotherapy plus PBRT. The 3-year progression-free survival rate was 41% for all 24 patients undergoing PBRT and 36% for the 16 patients undergoing MTX-based chemotherapy. The in-field recurrence rate was 26% and the out-of-field recurrence rate was 15% at 3 years for all 24 patients undergoing PBRT. The rates for in-field recurrence and the out-of-field recurrence were 27% and 21%, respectively, for the 16 patients undergoing MTX-based chemotherapy. CNS-recurrence rates were similar in patients undergoing MTX-based chemotherapy and PBRT to the rates in those undergoing MTX-based chemotherapy and WBRT. Neurocognitive dysfunction developed in 3 of the 16 patients undergoing MTX + PBRT and in 4 of 15 patients undergoing MTX + WBRT (P = 0.68). PBRT seems to be a feasible treatment option for solitary PCNSL. Further investigations are warranted to evaluate the advantages of PBRT over WBRT.

Development of system using beam's eye view images to measure respiratory motion tracking errors in image-guided robotic radiosurgery system.

The accuracy of the CyberKnife Synchrony Respiratory Tracking System (SRTS) is considered to be patient-dependent because the SRTS relies on an individual correlation between the internal tumor position (ITP) and the external marker position (EMP), as well as a prediction method to compensate for the delay incurred to adjust the position of the linear accelerator (linac). We aimed to develop a system for obtaining pretreatment statistical measurements of the SRTS tracking error by using beam's eye view (BEV) images, to enable the prediction of the patient-specific accuracy. The respiratory motion data for the ITP and the EMP were derived from cine MR images obtained from 23 patients. The dynamic motion phantom was used to reproduce both the ITP and EMP motions. The CyberKnife was subsequently operated with the SRTS, with a CCD camera mounted on the head of the linac. BEV images from the CCD camera were recorded during the tracking of a ball target by the linac. The tracking error was measured at 15 Hz using in-house software. To assess the precision of the position detection using an MR image, the positions of test tubes (determined from MR images) were compared with their actual positions. To assess the precision of the position detection of the ball, ball positions measured from BEV images were compared with values measured using a Vernier caliper. The SRTS accuracy was evaluated by determining the tracking error that could be identified with a probability of more than 95% (Ep95). The detection precision of the tumor position (determined from cine MR images) was < 0.2 mm. The detection precision of the tracking error when using the BEV images was < 0.2mm. These two detection precisions were derived from our measurement system and were not obtained from the SRTS. The median of Ep95 was found to be 1.5 (range, 1.0-3.5) mm. The difference between the minimum and maximum Ep95 was 2.5mm, indicating that this provides a better means of evaluating patient-specific SRTS accuracy. A suitable margin, based on the predicted patient-specific SRTS accuracy, can be added to the clinical target volume.

Dose-volume histogram comparison between static 5-field IMRT with 18-MV X-rays and helical tomotherapy with 6-MV X-rays.

We treated prostate cancer patients with static 5-field intensity-modulated radiation therapy (IMRT) using linac 18-MV X-rays or tomotherapy with 6-MV X-rays. As X-ray energies differ, we hypothesized that 18-MV photon IMRT may be better for large patients and tomotherapy may be more suitable for small patients. Thus, we compared dose-volume parameters for the planning target volume (PTV) and organs at risk (OARs) in 59 patients with T1-3 N0M0 prostate cancer who had been treated using 5-field IMRT. For these same patients, tomotherapy plans were also prepared for comparison. In addition, plans of 18 patients who were actually treated with tomotherapy were analyzed. The evaluated parameters were homogeneity indicies and a conformity index for the PTVs, and D2 (dose received by 2% of the PTV in Gy), D98, Dmean and V10-70 Gy (%) for OARs. To evaluate differences by body size, patients with a known body mass index were grouped by that index ( <21; 21-25; and >25 kg/m(2)). For the PTV, all parameters were higher in the tomotherapy plans compared with the 5-field IMRT plans. For the rectum, V10 Gy and V60 Gy were higher, whereas V20 Gy and V30 Gy were lower in the tomotherapy plans. For the bladder, all parameters were higher in the tomotherapy plans. However, both plans were considered clinically acceptable. Similar trends were observed in 18 patients treated with tomotherapy. Obvious trends were not observed for body size. Tomotherapy provides equivalent dose distributions for PTVs and OARs compared with 18-MV 5-field IMRT. Tomotherapy could be used as a substitute for high-energy photon IMRT for prostate cancer regardless of body size.

[Severe bortezomib-induced peripheral neuropathy in a patient with multiple myeloma].

A 59-year-old man was diagnosed with IgA-kappa multiple myeloma in October 2005. He was treated with 4 courses of VAD and autologous peripheral blood stem cell transplantation (auto-PBSCT) after 200 mg/m(2) melphalan in September 2006, followed by a second auto-PBSCT after 200 mg/m(2) melphalan in February 2007. However, he did not achieve a very good partial response (VGPR). Laboratory examinations showed increased serum IgA level and renal dysfunction gradually progressed. Bortezomib was then started at a dose of 1.3 mg/m(2) in November 2008. After three cycles of bortezomib, the patient developed numbness, pain and weakness of his upper and lower extremities. The sensation of position and vibration was diminished in the fingers and toes. He developed left foot drop and gait disturbance due to left peroneal nerve palsy. Autonomic dysfunction such as orthostatic hypotension and urinary retention also occurred. Nerve conduction studies showed severe sensorimotor polyneuropathy particularly in the lower extremities. He developed grade 4 motor neuropathy and severe painful neuralgia. Six months after the cessation of bortezomib, these symptoms gradually improved and he was able to walk with support and discharged. Close monitoring of neurological symptoms and prompt dose-reduction or cessation of bortezomib are important to prevent the progression of irreversible peripheral neuropathy.