Chisa Hashizume

Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer: a multicenter study.

The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days.

Stereotactic Body Radiotherapy Using a Radiobiology-Based Regimen for Stage I Non–Small-Cell Lung Cancer: Five-Year Mature Results

Introduction: Although the protocol of 48 Gy in four fractions over 4 days has been most often employed in stereotactic body radiotherapy (SBRT) for stage I non–small-cell lung cancer in Japan, higher doses are necessary to control larger tumors, and interfraction intervals should be longer than 24 hours to take advantage of reoxygenation. We report the final results of our study testing the following regimen: for tumors less than 1.5, 1.5–3, and greater than 3 cm in diameter, 44, 48, and 52 Gy, respectively, were given in four fractions with interfraction intervals of greater than or equal to 3 days. Methods: Among 180 histologically proven patients entered, 120 were medically inoperable and 60 were operable. The median patient age was 77 years (range, 29–89). SBRT was performed with 6-MV photons using four noncoplanar and three coplanar beams. Isocenter doses of 44, 48, and 52 Gy were given to four, 124, and 52 patients, respectively. Results: The 5-year overall survival rate was 52.2% for all 180 patients and 66% for 60 operable patients. The 5-year local control rate was 86% for tumors less than or equal to 3 cm (44/48 Gy) and 73% for tumors greater than 3 cm (52 Gy; p = 0.076). Grade greater than or equal to 2 radiation pneumonitis developed in 13% (10% for the 44/48-Gy group and 21% for the 52-Gy group; p = 0.056). Other grade 2 toxicities were all less than 4%. Conclusions: Our first prospective SBRT study yielded reasonable local control and overall survival rates and acceptable toxicity. Refinement of the protocol including dose escalation may lead to better outcome.

Assessment of spatial uncertainties in the radiotherapy process with the Novalis system.

PURPOSE The purpose of this study was to evaluate the accuracy of a new version of the ExacTrac X-ray (ETX) system with statistical analysis retrospectively in order to determine the tolerance of systematic components of spatial uncertainties with the Novalis system. METHODS AND MATERIALS Three factors of geometrical accuracy related to the ETX system were evaluated by phantom studies. First, location dependency of the detection ability of the infrared system was evaluated. Second, accuracy of the automated calculation by the image fusion algorithm in the patient registration software was evaluated. Third, deviation of the coordinate scale between the ETX isocenter and the mechanical isocenter was evaluated. From the values of these examinations and clinical experiences, the total spatial uncertainty with the Novalis system was evaluated. RESULTS As to the location dependency of the detection ability of the infrared system, the detection errors between the actual position and the detected position were 1% in translation shift and 0.1 degrees in rotational angle, respectively. As to the accuracy of patient verification software, the repeatability and the coincidence of the calculation value by image fusion were good when the contrast of the X-ray image was high. The deviation of coordinates between the ETX isocenter and the mechanical isocenter was 0.313 +/- 0.024 mm, in a suitable procedure. CONCLUSIONS The spatial uncertainty will be less than 2 mm when suitable treatment planning, optimal patient setup, and daily quality assurance for the Novalis system are achieved in the routine workload.

Progression of Non-Small-Cell Lung Cancer During the Interval Before Stereotactic Body Radiotherapy

PURPOSE To investigate the relationship between waiting time (WT) and disease progression in patients undergoing stereotactic body radiotherapy (SBRT) for lung adenocarcinoma (AD) or squamous cell carcinoma (SQ). METHODS AND MATERIALS 201 patients with Stage I AD or SQ undergoing SBRT between January 2004 and June 2010 were analyzed. The WT was defined as the interval between diagnostic computed tomography before referral and computed tomography for treatment planning or positioning before SBRT. Tumor size was measured on the slice of the longest tumor diameter, and tumor volume was calculated from the longest diameter and the diameter perpendicular to it. Changes in tumor volume and TNM stage progression were evaluated, and volume doubling time (VDT) was estimated. RESULTS The median WT was 42 days (range, 5-323 days). There was a correlation between WT and rate of increase in volume in both AD and SQ. The median VDTs of AD and SQ were 170 and 93 days, respectively. Thirty-six tumors (23%) did not show volume increase during WTs >25 days. In 41 patients waiting for ≤4 weeks, no patient showed T stage progression, whereas in 25 of 120 (21%) patients waiting for >4 weeks, T stage progressed from T1 to T2 (p = 0.001). In 10 of 110 (9.1%) T1 ADs and 15 of 51 (29%) T1 SQs, T stage progressed (p = 0.002). N stage and M stage progressions were not observed. CONCLUSION Generally, a WT of ≤4 weeks seems to be acceptable. The WT seems to be more important in SQ than in AD.

Hypofractionated Stereotactic Body Radiotherapy for Primary and Metastatic Liver Tumors Using the Novalis Image-Guided System: Preliminary Results regarding Efficacy and Toxicity

The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrences criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

Increases in the number of brain metastases detected at frame-fixed, thin-slice MRI for gamma knife surgery planning

For gamma knife planning, 2.4-mm-slice MRIs are taken under rigid frame fixation, so tiny tumors become visible. This study evaluated differences in the numbers of brain metastases between conventional contrast-enhanced MRI (6 ± 1 mm slice thickness) taken before patient referral and contrast-enhanced MRI for gamma knife planning. The numbers of metastases on the 2 images were counted by at least 2 oncologists. For gamma knife planning, spoiled gradient-recalled echo images were obtained after 0.1 mmol/kg gadolinium administration using a 1.5-T system. Images from 1045 patients with an interval between the 2 MRI studies of 6 weeks or less were analyzed. Increases in the number of metastases were found in 33.7% of the 1045 patients, whereas the number was identical in 62.3%. In 4.0%, the number decreased, indicating overdiagnosis at conventional MRI. These proportions did not differ significantly by the interval before gamma knife. An increase from single to multiple metastases was found in 16.0%. Meningeal dissemination was newly diagnosed in 2.3%. On planning images, the proportions of patients with 1, 2, 3, and 4 or more lesions were 37.6%, 19.3%, 9.3%, and 33.8%, respectively. In cases of colorectal cancer and hepatoma, the proportions of patients with a single metastasis (32 of 61 [52%] and 5 of 6 [83%], respectively) were higher than that of patients with other malignancies. In about one-third of the patients, an increased number of metastases were found on the thin-slice images. This should be kept in mind when deciding the treatment strategy for brain metastases.

Gamma Knife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas

BACKGROUND Non-benign meningioma has a known trend to recur repeatedly. The results of Gamma Knife stereotactic radiosurgery (GKS) for recurrent or residual atypical and malignant meningiomas are reported. METHODS Thirty patients (13 men, 17 women) with World Health Organization (WHO) grade II (24 cases) or grade III (6 cases) intracranial meningiomas underwent GKS. Their age varied from 30 to 86 years (mean 64 years). Before GKS, the tumor was surgically resected in all patients, and 11 of them also underwent conventional external beam radiation therapy, LINAC-based stereotactic radiotherapy (SRT), or intensity-modulated radiation therapy. FINDINGS Of the 30 patients, 23 were followed after the initial GKS for a median period of 28 months (range 2-135 months). Local tumor control after treatment was 74 % at 1 year, 52 % at 2 years, and 34 % at 3 years. A total of 15 patients underwent repeat GKS (one to nine times) because of local or distant intracranial tumor progression, seven were subjected to surgical re-resection of the neoplasm, and four had additional SRT. At the time of the last follow-up, 21 patients were alive, and 2 had died. One of the latter expired because of brain tumor progression at 91 months after the initial GKS, and the other patient died from lung cancer. CONCLUSIONS Although atypical and malignant meningiomas have a trend to recur repeatedly, aggressive tumor management with repeat GKS at the time of progression can provide long survival in these patients.

Early response and local control of stage I non-small-cell lung cancer after stereotactic radiotherapy: difference by histology

To investigate the possible influences of various factors on tumor response to radiation, regression speeds and long‐term local control rates of primary adenocarcinoma and squamous cell carcinoma of the lung after stereotactic body radiotherapy were evaluated. Ninety‐one patients (65 men and 26 women) with a median age of 76 years were serially examined using computed tomography at 2, 4 and 6 months after treatment. Tumor histology was adenocarcinoma in 62 patients and squamous cell carcinoma in 29 patients. The prescribed dose was 48 Gy in four fractions given twice a week for T1 tumors (≤3 cm) and 52 Gy in four fractions given twice a week for T2 tumors (3–5 cm). Tumor shrinkage speed and 3‐year local control rates were similar between T1 and T2 tumors and between patients with normal pulmonary function and those with impaired function. Squamous cell carcinomas shrank faster than adenocarcinomas at 2 and 4 months after radiation, but mean relative tumor size at 6 months and local control rates at 3 years did not differ significantly between the two histologies. Tumors in patients with a higher hemoglobin level tended to shrink faster but the control rates were not different. It is concluded that, although squamous cell carcinoma shrinks faster than adenocarcinoma, the two types of lung cancer are of similar radiosensitivity in terms of long‐term control rates. Radiosensitivity should not be evaluated by early tumor response. (Cancer Sci 2013; 104: 130–134)

Radiotherapy for hilar or mediastinal lymph node metastases after definitive treatment with stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer

PURPOSE Management of regional lymph node (LN) recurrence is an important issue in definitive treatment of non-small cell lung cancer (NSCLC). We evaluated clinical outcomes of conventional radiotherapy for hilar or mediastinal LN metastases developing after stereotactic body radiotherapy (SBRT) or surgery for stage I NSCLC. METHODS AND MATERIALS Between 2004 and 2008, 26 patients with hilar or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 12) were treated with conventional radiotherapy. Twelve of the 14 post-SBRT patients (86%) were judged medically inoperable at the time of SBRT. All patients were treated to the hilum and mediastinum with conventional daily fractions of 2.0 Gy (n = 25) or 2.4 Gy (n = 1). The median total dose for treating metastatic LN was 60 Gy (range, 54-66 Gy) for the post-SBRT patients and 65 Gy (range, 60-66 Gy) for the post-surgery patients. Only 1 of the 14 post-SBRT patients and 8 of the 12 post-surgery patients received chemotherapy. RESULTS For all 26 patients, the overall and cause-specific survival rates at 3 years from radiation for LN metastases were 36% and 51%, respectively (14% and 39%, respectively, for the 14 post-SBRT patients and both 64% for the 12 post-surgery patients). Three of the SBRT patients were alive at 35 to 43 months with (n = 2) or without (n = 1) further recurrence, and 4 of the post-surgery patients were alive at 36 to 62 months with (n = 2) or without (n = 2) further recurrence. The incidence of ≥grade 2 pulmonary toxicity was 49% at 1 year (53% for post-SBRT patients and 44% for post-surgery patients). A grade 5 pulmonary toxicity was observed in 1 of the post-SBRT patients. CONCLUSIONS Conventional radiotherapy could successfully salvage LN relapses after SBRT as well as after surgery in 7 of 26 patients. Radiotherapy in this setting appears reasonably well tolerated.

Validation of accuracy in image co-registration with computed tomography and magnetic resonance imaging in Gamma Knife radiosurgery

The latest version of Leksell GammaPlan (LGP) is equipped with Digital Imaging and Communication in Medicine (DICOM) image-processing functions including image co-registration. Diagnostic magnetic resonance imaging (MRI) taken prior to Gamma Knife treatment is available for virtual treatment pre-planning. On the treatment day, actual dose planning is completed on stereotactic MRI or computed tomography (CT) (with a frame) after co-registration with the diagnostic MRI and in association with the virtual dose distributions. This study assesses the accuracy of image co-registration in a phantom study and evaluates its usefulness in clinical cases. Images of three kinds of phantoms and 11 patients are evaluated. In the phantom study, co-registration errors of the 3D coordinates were measured in overall stereotactic space and compared between stereotactic CT and diagnostic CT, stereotactic MRI and diagnostic MRI, stereotactic CT and diagnostic MRI, and stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. In the clinical study, target contours were compared between stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. The mean errors of coordinates between images were < 1 mm in all measurement areas in both the phantom and clinical patient studies. The co-registration function implemented in LGP has sufficient geometrical accuracy to assure appropriate dose planning in clinical use.