A. Miyakawa

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.

Clinical outcomes of stereotactic body radiotherapy for stage I non-small cell lung cancer using different doses depending on tumor size

BackgroundThe treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter.MethodsBetween February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions.ResultsFor all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02).ConclusionsThere was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further.

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.

Applicability of the linear–quadratic model to single and fractionated radiotherapy schedules: an experimental study

The aim of this study was to examine the applicability of the linear-quadratic (LQ) model to single and fractionated irradiation in EMT6 cells. First, the α/β ratio of the cells was determined from single-dose experiments, and a biologically effective dose (BED) for 20 Gy in 10 fractions (fr) was calculated. Fractional doses yielding the same BED were calculated for 1-, 2-, 3-, 4-, 5-, 7-, 15- and 20-fraction irradiation using LQ formalism, and then irradiation with these schedules was actually given. Cell survival was determined by a standard colony assay. Differences in cell survival between pairs of groups were compared by t-test. The α/β ratio of the cells was 3.18 Gy, and 20 Gy in 10 fr corresponded to a BED3.18 of 32.6 Gy. The effects of 7-, 15- and 20-fraction irradiation with a BED3.18 of 32.6 Gy were similar to those of the 10-fraction irradiation, while the effects of 1- to 5-fraction irradiation were lower. In this cell line, the LQ model was considered applicable to 7- to 20-fraction irradiation or doses per fraction of 2.57 Gy or smaller. The LQ model might be applicable in the dose range below the α/β ratio.

Correlation between the serum KL-6 level and the grade of radiation pneumonitis after stereotactic body radiotherapy for stage I lung cancer or small lung metastasis.

0167-8140/

Percutaneous fiducial marker placement under CT fluoroscopic guidance for stereotactic body radiotherapy of the lung: an initial experience

see front matter 2011 Elsevier Irelan doi:10.1016/j.radonc.2011.05.031 ⇑ Corresponding author. Address: Department of Ra sity Graduate School of Medical Sciences, 1 Kawasu Nagoya 467-8601, Japan. E-mail address: h-iwa-ncu@nifty.com (H. Iwata). Serum levels of a sialylated carbohydrate antigen KL-6, a marker for interstitial pneumonitis, were serially measured before and after stereotactic body radiotherapy (SBRT) for lung tumors. It was suggested that KL-6 levels before and after SBRT would help to predict the occurrence of P Grade 2 radiation pneumonitis. 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 267–270

Organizing pneumonia after stereotactic ablative radiotherapy of the lung.

The aim of this study is to describe our initial experience with the VISICOIL, which is the first percutaneous fiducial marker approved for stereotactic body radiotherapy in Japan, and to evaluate its technical and clinical efficacy, and safety. Eight patients underwent this procedure under CT fluoroscopic guidance. One patient had two tumors, so the total number of procedures was nine. We evaluated the technical and clinical success rates of the procedure and the frequencies of complications. Technical success was defined as when the fiducial marker could be placed at the target site, and clinical success was defined as when stereotactic body radiotherapy could be performed without the marker dropping out of position. The technical success rate was 78% (7/9). In one of the two failed cases, we aimed to place the marker inside the tumor, but misplaced it beside the tumor. In the other failed case, we successfully placed the marker beside the tumor as planned; however, the marker migrated to near the pleura after the patient stopped holding their breath. None of the markers dropped out of place, so the clinical success rate was 100% (9/9). The complication rates were as follows: pneumothorax: 56% (5/9), pneumothorax necessitating chest tube placement: 44% (4/9), focal intrapulmonary hemorrhaging: 67% (6/9), hemoptysis: 11% (1/9), mild hemothorax 11% (1/9), air embolism 0% (0/9), and death 0% (0/9). In conclusion, this new percutaneous fiducial marker appears to be useful for stereotactic body radiotherapy due to its good stability.

Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?

BackgroundOrganizing pneumonia (OP), so called bronchiolitis obliterans organizing pneumonia after postoperative irradiation for breast cancer has been often reported. There is little information about OP after other radiation modalities. This cohort study investigated the clinical features and risk factors of OP after stereotactic ablative radiotherapy of the lung (SABR).MethodsPatients undergoing SABR between 2004 and 2010 in two institutions were investigated. Blood test and chest computed tomography were performed at intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1) mixture of patchy and ground-glass opacity, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume receiving < 0.5 Gy, and 4) no evidence of a specific cause.ResultsAmong 189 patients (164 with stage I lung cancer and 25 with single lung metastasis) analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These symptoms and pulmonary infiltration rapidly improved after corticosteroid therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP) around the tumor 2 to 7 months before OP. The prior RP history was strongly associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis.ConclusionsThis is the first report on OP after SABR. The incidence appeared to be relatively high. The symptoms were sometimes severe, but corticosteroid therapy was effective. When patients after SABR present with unusual pneumonia, OP should be considered as a differential diagnosis, especially in patients with prior symptomatic RP.

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

In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter.

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

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)