Stereotactic radiotherapy of primary liver cancer and hepatic metastases.

The purpose was to evaluate the clinical results of stereotactic radiotherapy in primary liver tumors and hepatic metastases. Five patients with primary liver cancer and 39 patients with 51 hepatic metastases were treated by stereotactic radiotherapy since 1997. Twenty-eight targets were treated in a "low-dose"-group with 3 x 10 Gy (n = 27) or 4 x 7 Gy (n = 1) prescribed to the PTV-encl. 65%-isodose. In a "high-dose"-group patients were treated with 3 x 12 - 12.5 Gy (n = 19; same dose prescription) or 1 x 26 Gy/PTV-enclosing 80%-isodose (n = 9). Median follow-up was 15 months (2-48 months) for primary liver cancer and 15 months (2-85 months) for hepatic metastases. While all primary liver cancers were controlled, nine local failures (3-19 months) of 51 metastases were observed resulting in an actuarial local control rate of 92% after 12 months and 66% after 24 months and later. A borderline significant correlation between dose and local control was observed (p = 0.077): the actuarial local control rate after 12 and 24 months was 86% and 58% in the low-dose-group versus 100% and 82% in the high-dose-group. In multivariate analysis high versus low-dose was the only significant factor predicting local control (p = 0.0089). Overall survival after 1 and 2 years was 72% and 32% for all patients and was impaired due to systemic progression of disease. No severe acute or late toxicity exceeding RTOG/EORTC-score 2 were observed. Stereotactic irradiation of primary liver cancer and hepatic metastases offers a locally effective treatment without significant complications in patients, who are not amenable for surgery. Patient selection is important, because those with low risk for systemic progression are more likely to benefit from this approach.

Boost radiotherapy in young women with ductal carcinoma in situ: a multicentre, retrospective study of the Rare Cancer Network.

BACKGROUND: Outcome data in young women with ductal carcinoma in situ (DCIS) are rare. The benefits of boost radiotherapy in this group are also unknown. We aimed to assess the effect of boost radiotherapy in young patients with DCIS. METHODS: We included 373 women from 18 institutions who met the following inclusion criteria: having tumour status Tis and nodal status (N)0, age 45 years or younger at diagnosis, and having had breast-conserving surgery. 57 (15%) patients had no radiotherapy after surgery, 166 (45%) had radiotherapy without boost (median dose 50 Gy [range 40-60]), and 150 (40%) had radiotherapy with boost (60 Gy [53-76]). The primary outcome was local relapse-free survival. FINDINGS: Median follow-up was 72 months (range 1-281). 55 (15%) patients had local relapse. Local relapse-free survival at 10 years was 46% (95% CI 24-67) for patients given no radiotherapy, 72% (61-83) for those given radiotherapy without boost, and 86% (78-93) for those given radiotherapy and boost (difference between all three groups, p<0.0001). Age, margin status, and radiotherapy dose were significant predictors of local relapse-free survival. Compared with patients who had no radiotherapy, those who had radiotherapy had a decreased risk of local relapse (without boost, hazard ratio 0.33 [95% CI 0.16-0.71], p=0.004; with boost, 0.15 [0.06-0.36], p<0.0001). INTERPRETATION: In the absence of randomised trials, boost radiotherapy should be considered in addition to surgery for breast-conserving treatment for DCIS.

Radiation induced DNA damage and damage repair in human tumor and fibroblast cell lines assessed by histone H2AX phosphorylation.

PURPOSE: To analyze the radiation-induced levels of gammaH2AX and its decay kinetics in 10 human cell lines covering a wide range of cellular radiosensitivity (SF2, 0.06-0.63). METHODS AND MATERIALS: Five tumor cell lines included Colo-800 melanoma, two glioblastoma (MO59J and MO59K), fibrosarcoma HT 1080, and breast carcinoma MCF7. Five primary skin fibroblasts lines included two normal strains, an ataxia telangiectasia strain, and two fibroblast strains from breast cancer patients with an adverse early skin reaction to radiotherapy. Cellular radiosensitivity was assessed by colony-forming test. Deoxyribonucleic acid damage and repair were analyzed according to nuclear gammaH2AX foci intensity, with digital image analysis. RESULTS: The cell lines tested showed a wide degree of variation in the background intensity of immunostained nuclear histone gammaH2AX, which was higher for the tumor cell lines compared with the fibroblast strains. It was not possible to predict clonogenic cell survival (SF2) for the 10 cell lines studied from the radiation-induced gammaH2AX intensity. In addition, the slopes of the dose-response (0-4 Gy) curves, the rates of gammaH2AX disappearance, and its residual expression (

Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients.

PURPOSE: The clinical results of dose escalation using stereotactic radiotherapy to increase local tumor control in medically inoperable patients with Stage I-II non-small-cell lung cancer or pulmonary metastases were evaluated. METHODS AND MATERIALS: Twenty patients with Stage I-II non-small-cell lung cancer and 41 patients with 51 pulmonary metastases not amenable to surgery were treated with stereotactic radiotherapy at 3 x 10 Gy (n = 19), 3 x 12-12.5 Gy to the planning target volume enclosing 100%-isodose, with normalization to 150% at the isocenter; n = 26) or 1 x 26 Gy to the planning target volume enclosing 80%-isodose (n = 26). The median follow-up was 11 months (range, 2-61 months) for primary lung cancer patients and 9 months (range, 2-37 months) for patients with metastases. RESULTS: The actuarial local control rate was 92% for lung cancer patients and 80% for metastasis patients > or =1 year after treatment and was significantly improved by increasing the dose from 3 x 10 Gy to 3 x 12-12.5 Gy or 1 x 26 Gy (p = 0.038). The overall survival rate after 1 and 2 years was 52% and 32%, respectively, for lung cancer patients and 85% and 33%, respectively, for metastasis patients, impaired because of systemic disease progression. After 12 months, 60% of patients with primary lung cancer and 35% of patients with pulmonary metastases were without systemic progression. No severe acute or late toxicity was observed, and only 2 patients (3%) developed symptomatic Grade 2 pneumonitis, which was successfully treated with oral steroids. CONCLUSION: Stereotactic radiotherapy for lung tumors offers a very effective treatment option locally without significant complications in medically impaired patients who are not amenable to surgery. Patient selection is important, because those with a low risk of systemic progression are more likely to benefit from this approach.

Positional variability of a tandem applicator system in HDR brachytherapy for primary treatment of cervix cancer. Analysis of the anatomic pelvic position and comparison of the applicator positions during five insertions.

PURPOSE: Evaluation of the inter- and intraindividual applicator variability of multiple high-dose-rate (HDR) brachytherapy applications for primary treatment of cancer of the uterine cervix. MATERIAL AND METHODS: Retrospective analysis of 460 pairs of orthogonal X-ray films for conventional treatment in 92 patients with five intrauterine applications using an HDR tandem applicator. Measurement of the position of the applicator origin relative to a bony reference system in three dimensions. Evaluation of the differences of the applicator position in all 460 applications (interindividual variability), of the five applications in a single patient (intraindividual variability) and of the intraindividual variability relative to the applicator position at the first application. RESULTS: The position of the applicator origin in the pelvis ranged from 23 mm cranial and 55 mm caudal to the top of femoral heads, 23 mm right and 27 mm left to the pelvic midline, and 6-53 mm dorsal to the mid of the femoral heads. Standard deviation (SD) of interindividual applicator variability was 12.9 mm (minimum/maximum -55/+23 mm, mean -13.6 mm) in longitudinal, 5.1 mm (-27/+23 mm, mean 1.6 mm) in lateral, and 7.6 mm (6/53 mm, mean 26 mm) in anterior-posterior [AP] direction. SD of intraindividual variability was 5.5 mm (-21/+23 mm, mean 0 mm) in longitudinal, 2.5 mm (-17/+19 mm, mean 0 mm) in lateral, and 4.2 mm (-15/+18 mm, mean 0 mm) in AP direction compared to intraindividual variability relative to the first insertion with an SD of 8.9 mm (-23/+36 mm, mean 2.8 mm) in longitudinal, 4.0 mm (-11/+23 mm, mean 0 mm) in lateral, and 6.8 mm (-27/+17 mm, mean -0.8 mm) in AP direction. CONCLUSION: Intraindividual applicator variability is significantly smaller than interindividual variability. Applicator-related procedures such as midline shielding or dose matching of tele- and brachytherapy should be performed with information on at least one individual applicator position.

Stereotactic boost irradiation for targets in the abdomen and pelvis.

Based on the experience of stereotactic irradiation of lung and liver tumors the feasibility of stereotactic boost irradiation to abdominal and pelvic tumors was evaluated. Twenty-one patients with inoperable tumors received a stereotactic boost of 2-3 x 5Gy/PTV-enclosing-100% isodose with normalization to 150% at the isocenter after normofractionated irradiation of 45-50.4Gy. Actuarial local control (16/21 targets) was 96/70% after 12 and 24 months. Treatment was feasible and well tolerated.

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.