Stereotactic Radiotherapy Dose Research Articles

Phase I trial combining ipilimumab + high dose stereotactic radiation: Results and serum immune correlates.

3022Background: Preclinical models suggest systemic disease control with ipilimumab (IPI) and radiation. Here we conducted a phase I trial of IPI and high dose stereotactic body radiation therapy (...

PV-0176: Evaluation of biologically effective dose in stereotactic radiotherapy for prostate cancer

PV-0176: Evaluation of biologically effective dose in stereotactic radiotherapy for prostate cancer

EP-1649: Lung dose in stereotactic radiotherapy for lung tumors delivered with VMAT

EP-1649: Lung dose in stereotactic radiotherapy for lung tumors delivered with VMAT

Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration: Year 2 Results of the INTREPID Study

To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD). Randomized, double-masked, sham-controlled, multicenter, clinical trial. A total of 230 participants with neovascular AMD who received ≥ 3 ranibizumab or bevacizumab injections within the preceding year and requiring treatment at enrollment. Participants received 16 Gray, 24 Gray, or sham SRT. All arms received pro re nata (PRN) ranibizumab for 12 months, with PRN bevacizumab or ranibizumab thereafter. Mean number of PRN injections; best-corrected visual acuity (BCVA); loss of <15 Early Treatment of Diabetic Retinopathy Study letters; change in optical coherence tomography central subfield thickness; and change in angiographic total lesion area and choroidal neovascularization (CNV) area. At year 2, the 16 and 24 Gray arms received fewer PRN treatments compared with sham (mean 4.5, P = 0.008; mean 5.4, P = 0.09; and mean 6.6, respectively). Change in mean BCVA was -10.0, -7.5, and -6.7 letters for the 16 Gray, 24 Gray, and sham arms, respectively, with 46 (68%), 51 (75%), and 58 participants (79%), respectively, losing <15 letters. Mean central subfield thickness decreased by 67.0 μm, 55.4 μm, and 33.3 μm, respectively. Mean total active lesion area increased by 1.0, 4.2, and 2.7 mm(2), respectively. Mean CNV area decreased by 0.1 mm(2) in all groups. An independent reading center detected microvascular abnormalities in 6 control eyes and 29 SRT eyes, of which 18 were attributed to radiation; however, only 2 of these possibly affected vision. An exploratory subgroup analysis found that lesions with a greatest linear dimension ≤ 4 mm (the size of the treatment zone) and a macular volume greater than the median (7.4 mm(3)) were more responsive to SRT, with 3.9 PRN injections versus 7.1 in comparable sham-treated participants (P = 0.001) and mean BCVA 4.4 letters superior to sham (P = 0.24). A single dose of SRT significantly reduces intravitreal injections over 2 years. Radiation can induce microvascular change, but in only 1% of eyes does this possibly affect vision. The best response occurs when AMD lesions fit within the treatment zone and they are actively leaking.

Association Between Radiation Therapy Dose and Survival in Patients With Stage I Non-Small Cell Lung Cancer Undergoing Stereotactic Body Radiation Therapy

Purpose/Objective(s): Although stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is associated with high local control rates, the optimal dose-fractionation regimen is unknown, as prospective and retrospective data argue for different dosing paradigms. Whether increasing stereotactic radiation therapy dose can compensate for larger tumor volume is an open question. We aimed to determine the comparative effectiveness of different SBRT dosing regimens using a large national database, focusing on the relative impact of dose as a function of tumor stage. Materials/Methods: Patients in the National Cancer Database with clinical T1-2 N0 NSCLC who were treated with SBRT were eligible for inclusion in this cohort. Patient survival data were only available for those with a minimum of 5 years of follow-up, and therefore the analysis was restricted to those diagnosed between 2003 and 2006. Median follow-up and overall survival (OS) were defined from the date of diagnosis to last contact. The biologically equivalent dose (BED) was calculated based on the linear quadratic formula using an alpha/beta ratio of 10. All patients received a minimum BED of 70 Gy. Highversus lower-dose (HD vs LD) SBRT was defined as BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods. Cox proportional hazard multivariable analysis (MVA) was used to estimate hazard ratios (HR), adjusting for age, sex, T stage, BED, facility type (academic vs community practice), insurance status, year of diagnosis, comorbidities, race, and histology. Results: A total of 498 patients (T1 Z 67%, T2 Z 33%) met inclusion criteria. The median follow-up was 3 years (range, 3 months-8.6 years) for the entire cohort and 5.6 years for surviving patients. The 5 most common dose fractionation schemes (% of cohort) utilized were 20 Gy x 3 (34%), 12 Gy x 4 (16%), 18 Gy x 3 (10%), 15 Gy x 3 (10%), and 10 Gy x 5 (2.6%). The median BED was 150 Gy (inter-quartile range 106 Gy 166 Gy). The 3and 5-year overall survival for the entire cohort was 50% and 30%. The 3 year OS for T1 vs T2 disease was 61% vs 30% (log rank p < 0.0001). The 3 year OS for patients who received HD vs LD was 55% vs 46% (log rank pZ 0.03). On subset analysis of the T1 cohort, there was no association between BED and 3-year OS (61% vs 60% with HD vs LD, p Z 0.9). Among the T2 cohort, patients receiving HD experienced superior 3 year OS (37% vs 24%, p Z 0.01). On MVA, the only factors independently prognostic for mortality were female gender (HR Z 0.76, p Z 0.01), T1 tumor (HR Z 0.51, p Z 0.0001), and HD (HR Z 0.78, p Z 0.01). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I NSCLC suggests higher doses are associated with a significant survival benefit, especially in patients with a larger burden of disease. Prospective data are needed to determine the optimal dose-fractionation regimen as a function of tumor volume. Author Disclosure: M. Koshy: None. R. Malik: None. D.J. Sher: None.

Stereotactic Radiotherapy for Neovascular Age-related Macular Degeneration: 52-Week Safety and Efficacy Results of the INTREPID Study

To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (nvAMD). Randomized, double-masked, sham-controlled, multicenter, clinical trial. Two hundred thirty patients with onset of nvAMD within 3 years who received 3 or more injections of ranibizumab or bevacizumab within the preceding year and who needed continuing ranibizumab or bevacizumab treatment. Participants were randomized 2:1:2:1 to 16 Gy plus pro re nata (PRN) ranibizumab, sham 16 Gy plus PRN ranibizumab, 24 Gy plus PRN ranibizumab, or sham 24 Gy plus PRN ranibizumab, respectively. The primary efficacy end point was the mean number of ranibizumab injections at 52 weeks. Secondary end points were change in mean best-corrected visual acuity (VA), loss of fewer than 15 Early Treatment Diabetic Retinopathy Study letters, gain of 0 or more and 15 or more letters, and change in angiographic total lesion size and choroidal neovascularization (CNV) lesion size. Both the 16-Gy and 24-Gy SRT arms received significantly fewer ranibizumab treatments compared with the sham arms: mean number of treatments, 2.64 (median, 2), 2.43 (median, 2), and 3.74 (median, 3.5), respectively (P = 0.013 and P = 0.004, respectively, vs. sham). Change in mean VA was -0.28, +0.40, and -1.57 letters for the 16-Gy, 24-Gy, and sham arms, respectively. The 16-Gy, 24-Gy, and sham arms lost fewer than 15 letters in 93%, 89%, and 91% of eyes, respectively, with 53%, 57%, and 56% gaining 0 or more letters, respectively, and 4% gaining 15 letters or more in all arms. Mean total angiographic lesion area changed by -1.15 mm(2), +0.49 mm(2), and +0.75 mm(2), respectively; mean CNV lesion area decreased by 0.16 mm(2), 0.18 mm(2), and 0.10 mm(2), respectively. Optical coherence tomography central subfield thickness decreased by 85.90 μm, 70.39 μm, and 33.51 μm, respectively. The number of adverse events (AEs) and number of serious AEs (SAEs) were similar across arms. No AEs were attributed to radiation. No SAEs occurred in the study eye. A single dose of SRT significantly reduces ranibizumab retreatment for patients with nvAMD, with a favorable safety profile at 1 year. Whereas chronic nvAMD typically results in loss of VA over time, SRT is associated with relatively well-preserved VA over 1 year. Proprietary or commercial disclosure may be found after the references.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy

To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Clinical outcomes of single or oligo-fractionated stereotactic radiotherapy for head and neck tumors using micromultileaf collimator-based dynamic conformal arcs

To assess the clinical outcomes of single or oligo-fractionated stereotactic radiotherapy (SRT) using dynamic conformal arcs (DCA) for head and neck tumors (HNTs). Thirty-four consecutive patients with 35 lesions treated between 2005 and 2009 were retrospectively evaluated, of whom 85.7% had recurrent or metastatic disease, and 45.7 and 34.3% had previous radiotherapy and surgery, respectively. The median SRT dose was 22.3Gy (11.2-32.8) in 2-4 fractions with a median interval of 7days and 10.4Gy (9.2-12.4) in one fraction. SRT was combined with upfront conventionally fractionated RT in 48.6% of patients. The median follow-up periods were 18.4months (2-84.1) for the entire cohort and 49.6months for the survivors. The 1- and 2-year local control (LC) rates were 84.3 and 70.5%, with the 1- and 2-year overall survival (OS) rates of 78.6 and 51.6%. LC was significantly better for tumor volumes <25.6cm(3) (p=0.001). OS was significantly longer in patients without any disease outside the SRT site (p<0.001), whereas LC after the SRT did not affect the OS. Late adverse events occurred in 9 patients, including cranial nerve (CN) injury (grade 3/4) in 2, brain radionecrosis in 5 (grade 1), and fatal bleeding in 2 patients harboring uncontrolled lesions abutting the carotid artery. DCA-based SRT can confer relatively long-term LC with acceptable toxicity in selected patients with HNTs. The patients with CN involvement or tumor volume ≥25.6cm(3) were deemed unsuitable for this treatment regimen.

A Phase I Study of Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir as part of a Neoadjuvant Regimen in Patients with Locally Advanced Pancreatic Cancer

To perform a Phase I study of hypofractionated stereotactic radiotherapy (SRT) and concurrent HIV protease inhibitor Nelfinavir (radiation sensitizer) as part of a neoadjuvant regimen in patients with locally advanced pancreatic cancer and to determine the maximum tolerated SRT dose and the recommended SRT dose for Phase II study.

Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment With Linear Accelerator-Based Stereotactic Radiotherapy With Micromultileaf Collimator as Second-Line or Salvage Treatment After Chemotherapy

To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator. Between 2004 and 2008, 11 children (15 eyes) with macular and/or papillary retinoblastoma were treated with SRT. The mean age was 19 months (range, 2-111). Of the 15 eyes, 7, 6, and 2 were classified as International Classification of Intraocular Retinoblastoma Group B, C, and E, respectively. The delivered dose of SRT was 50.4 Gy in 28 fractions using a dedicated micromultileaf collimator linear accelerator. The median follow-up was 20 months (range, 13-39). Local control was achieved in 13 eyes (87%). The actuarial 1- and 2-year local control rates were both 82%. SRT was well tolerated. Late adverse events were reported in 4 patients. Of the 4 patients, 2 had developed focal microangiopathy 20 months after SRT; 1 had developed a transient recurrence of retinal detachment; and 1 had developed bilateral cataracts. No optic neuropathy was observed. Linear accelerator-based SRT for papillary and/or macular retinoblastoma in children resulted in excellent tumor control rates with acceptable toxicity. Additional research regarding SRT and its intrinsic organ-at-risk sparing capability is justified in the framework of prospective trials.

What is the Optimal Dose in Stereotactic Radiotherapy of Brain Metastases? A Systematic Literature Search

What is the Optimal Dose in Stereotactic Radiotherapy of Brain Metastases? A Systematic Literature Search

Clinical, dosimetric, and radiographic correlation of radiation injury involving the brainstem and the medial temporal lobes following stereotactic radiotherapy for neoplasms of central skull base

Stereotactic Radiotherapy (SRT) is more commonly used for skull base tumors in conjunction with the technical development of radiation intensity modulation. Purpose of this study is to correlate clinical and radiographic characteristics of delayed radiation injury (RI) occurring around central skull base following SRT with SRT dosimetric data. Total of six patients were identified to have developed RI in the vicinity of SRT target volume out of 141 patients who received SRT in he center or near-center of the skull base. The images and medical records were retrospectively reviewed. The analysis was performed for RI location, time of development, imaging and clinical characteristics and evolution of RI and correlated with SRT dosimetric analysis using image fusion with follow-up MRI scans. Mean follow-up time was 24 +/- 9 months. During the follow-up period, twelve sites of RI were found in 6 patients. They were clinically symptomatic in 4/6 patients (66.6%) at median 12.5 months after SRT. Mean time interval between SRT and detection of RI was 9 +/- 3, 18.5 +/- 5, and 13.5 months for brainstem, temporal lobe, and cerebellum/labyrinth lesions, respectively. All RI lesions were included in the region of high SRT doses. After steroid and symptomatic treatment, 50% of RI lesions showed complete response, and 40% showed partial response. RI can occur around the skull base because of irregular shape of target tumor, its close proximity to normal brain parenchyma, and inhomogeneity of dose distribution. Brainstem lesions occurred earlier than temporal lobe RI. The majority of the RI lesions, not mixed with the tumor in this study, showed radiographic and clinical improvement with steroid and symptomatic treatments.

Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis

X-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors. Between July 1999 and December 2004, a total of 122 intracranial lesions in 78 patients with BM were treated using SRT in our Center. Forty-nine patients had a solitary lesion and 29 had multiple (2-6) lesions. The median SRT dose was 15 Gy (11-24 Gy) in single fraction for 38 lesions, and 24 Gy (11-40 Gy) in 2-6 fractions for 84 lesions. SRT was combined with whole brain radiotherapy (WBRT) of 30-40 Gy for 39 patients. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox model, respectively. The median survival time was 12.9 months (1.7-77.4 months). The 1-year intracranial PFS rate was 87.4%. The 1-and 2-year OS rates were 53.9% and 25.8%, respectively. Univariate analysis showed that the 1-year OS rates were higher in the patients with pretreatment KPS of >/= 70, extracranial lesions controlled, or SRT combined with WBRT than in those with KPS of < 70 (60.7% vs. 29.4%, P = 0.002), extracranial lesions uncontrolled (69% vs. 44.9%, P = 0.005), or SRT alone (64.1% vs. 43.4%, P = 0.03). The benefit of treating with WBRT in combination was mainly achieved in the patients with extracranial lesions controlled or with more than one intracranial lesion. Multivariate analysis showed that KPS score and status of extracranial lesions were independent prognostic factors for OS. SRT is an effective and safe modality for BM. SRT combined with WBRT may prolong the survival time of the patients with extracranial lesions controlled or multiple intracranial lesions. Independent prognostic factors for OS are KPS score and status of extracranial lesions.

Excisional Biopsy followed by Intra-operative Seed Implant is a Promising Alternative to Stereotactic Radiotherapy (SRT) for Solitary Lung Cancer (SLC)

Obtaining tissue diagnosis is often challenging in patients with SLC who often have compromised pulmonary function. Percutaneous biopsy my cause pneumothorax and bleeding and pose a significant management dilemma. One option is to perform an excisional biopsy followed by IOSI once cancer diagnosis is confirmed. However, the clinical outcome of this approach has not been compared with SRT. This study was designed to compare IOSI and SRT. Forty four patients with SLC treated between 1999 and 2009 were evaluated. Twenty one patients received IOSI with I-125 seeds for 21 lesions and 23 patients received SRT to 24 lesions. The study subjects were evaluated for LC and distant metastasis (DM). Chi square test was employed to estimate significance. The median age of patients was 66 years and 76.5 years in IOSI and SRT group, respectively. In the IOSI group there were 90.4% patients with non–small cell lung cancer, 4.7% with small cell carcinoma and 4.7% with high-grade sarcoma. In the same group, 23.8% patients underwent lobectomy, 4.7% had a local excision of a sarcoma, and 57.1% underwent a wedge resection. The median number of I-125 seeds placed was 20.The median tumor size was 2.1 cm (range, 0.25–6 cm). The median activity of the seeds was 0.529mCi (range, 0.390–0.700mCi). The median follow-up was 7 months (range, 1–84 months). In the SRT group, 91.3% patients were non–small cell and 8.6% patients were metastatic carcinoma, 1 from an endometrial and 1 from parotid adenocarcinoma. The median tumor size in the SRT group was 1.5 cm (range, 0.3–4.8cm) and median follow-up was 12 months (Range, 2–72 months). SRT dose to 13/24 (54.1%) lesions was 30 Gy in 3 fractions, 4/24 (16.6%) lesions was 40 Gy in 4 fractions, 1/24 (4.1%) lesions was 50 Gy in 5 fractions, 1/24 (4.1%) lesions was 48 Gy in 4 fractions and 4/24 (16.6%) lesions was 60 Gy in 4 fractions. The LC in the IOSI group was 90.4% vs. 100% in the SRT group (p = 0.11). Distant failure as the first site of failure was observed in 4/23 (17.3%) patients in the IOSI group vs. 0/21 (0%) in the SRT group (p = 0.023). Four patients in the SRT group developed RTOG Grade II pneumonitis (RPN) (17.3%). No patients in the IOSI group developed RPN. There was 1 Grade II skin toxicity in the SRT group (4.3%). Both IOSI with I-125 seed implant and SRT produce high LC rates in patients with SLC. SRT resulted in fewer local recurrences (statistically non-significant) and fewer distant recurrences (statistically significant) when compared to IOSI. However, Patients undergoing SRT have a higher chance of developing Grade II pneumonitis and skin toxicity.

SU-FF-T-661: Investigating the Benefits of Stereotactic Light Ion Radiation Therapy for Treating Large Intracranial AVMs

Purpose The majority of complications occur in patients with large AVM volumes being treated with high doses. For large intracranial arteriovenous malformations, the special characteristics of high ionization density light ion beams offer several advantages over photon and proton beams for high dose stereotactic radiation therapy. These include a better depth dose‐distribution in tissue, negligible lateral scattering, a sharper penumbra, a steep dose fall‐off beyond the Bragg peak and a higher probability of vascular response. Material and Methods Peripheral doses and dose volume histograms (DVHs) of large AVMs were collected from different centers. Based on these data and using a maximum likelihood fitting, dose‐response parameters were derived for the Binomial model. A comparison was performed for different radiation modalities taking also into account their radiobiological differences. Results Light ion Bragg peak dose delivery has the precision required for treating very large AVMs, as well as for delivering extremely sharp focused beams to irregular lesions. For stereotactic radiosurgery with light ions, a better angiographic obliteration rate was observed. Furthermore, a lower complication rate and lower white matter necrosis was simultaneously achieved, which composed a more favorable overall clinical outcome. In patients treated by helium ion beams, a sharper dose‐response gradient was observed, which is probably related to a more homogenous radiosensitivity of the AVM nidus to ion beamradiation.Conclusion Based on this study of linear energy transfer of different therapeuticion beams19 (H, He, Li, C), Helium or Lithium ions may be most suitable for AVM's up to 10 cm3 and for larger AVMs Lithium to carbon ions may be more appropriate. The unique physical characteristics of light ion beams are of considerable advantage for the treatment of AVMs located in front of or adjacent to sensitive and functionally important brain structures.

Evaluation of pulmonary toxicity and efficacy of a radioprotector using MRI

18506 Background: Radiation induced pulmonary symptoms occur in 20% of patients who receive radiation treatment for cancer of the lung or breast. Presently, there is no clinical test available to predict symptomatic toxicity or to assess the extent of radiation induced lung injury early after treatment. We report the use of time-resolved magnetic resonance angiography (Tr-MRA) to assess the efficacy of a radioprotector in limiting radiation toxicity in a rabbit model of stereotactic radiation therapy (SRT) pulmonary injury. Methods: 10 rabbits were used, of these 4 received different radiation doses in 3 equal fractions of 7, 9, 11 or 13 Gy within a week and were intended to determine the minimum radiation dose capable of producing detectable injury using our MRA technique. Effects were measurable by MRA at the minimum dose of 9 Gy × 3 fractions. We irradiated the remaining rabbits with 3 × 11 Gy. Four of these animals received 50mg/Kg of the radioprotector amifostine, 20 min. before each SRT dose to the right lung delivered on a TomoTherapy scanner. Tr-MRA was performed using a 1.5T clinical MR scanner at baseline, 4, 8 weeks post SRT. A 3D FLASH sequence was used with 6 slices; resolution 1.4 × 1.1 × 12mm3; TR/TE = 3.3/1.2 ms; total time = 32 sec. A 3 cc injection of a Gd chelate was delivered after 2 sec. of the start. Perfusion changes were calculated from the subtracted MIP images and correlated over the multiple time points. Results: The mean baseline areas of perfused tissue were 12±1.6 cm2 (mean±STD) for the right lung (RL) and 9±1.1 cm2 for the left lung (LL). At 4 weeks post treatment, the three control rabbits (3 × 11 Gy and no radioprotector) had mean perfused areas of 9±2.1 cm2 for the RL and 10±0.5 cm2 for the LL. At the same time point, the animals that received the same radiation dose plus the radioprotector had mean perfused areas of 12±1.2 cm2 for RL and 10±0.3 cm2 for the LL. At 8 weeks post treatment, the control rabbits had obvious perfusion defects in the irradiated zone, with mean perfused areas of 7±2.3 cm2 (RL) and 9±0.1 cm2 (LL). At this time point the animals that received the radioprotector had mean values of 10±0.8 cm2 (RL) and 9±0.6 cm2 (LL). Conclusions: Tr-MRA detected radiation induced pulmonary injury 4 weeks post treatment and was able to detect reduced early treatment toxicity as a result of a clinically used radioprotector. No significant financial relationships to disclose.

2470: Characteristics of FDG-PET Images After Stereotactic Radiotherapy for Lung Cancer

The objective of this study was to evaluate characteristics of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images after stereotactic radiotherapy (SRT) for lung cancer. Thirty-four scans in 25 patients who underwent SRT for primary lung cancer and were free from local progression were enrolled into this study. The prescription dose of SRT was 48 Gy in 4 fractions at the isocenter. The FDG-PET scans were classified into an early-evaluated group (within 6 months after the completion of SRT) and a late-evaluated group (6 months or more after SRT). Uptakes on pulmonary regions to which high doses were delivered were evaluated quantitatively and qualitatively. Quantitative evaluation consisted of measurement of maximal standardized uptake values (SUVmax) in the regions. Qualitative evaluation consisted of visual analyses of intensity of the FDG uptakes compared with the blood pool (faint, intermediate or high) and demarcation of the uptakes (well-defined or ill-defined). The figure shows the SUVmax plotted in relation to months after SRT. The SUVmax were 4.0 ± 2.2 and 2.6 ± 1.0 (mean ± standard deviation) in the early-evaluated group and in the late-evaluated group, respectively. The difference in the mean SUVmax between the two groups was significant (P = 0.032 by Welch’s test). The results of the visual analyses were shown in the table.Tabled 1The results of the visual analysesEarly (<6 mo)Late (≥6 mo)IntensityFaint6.3%22.2%P = 0.088Intermediate43.8%61.1%High50.0%16.7%DemarcationWell-defined75.0%33.3%P = 0.037Ill-defined25.0%66.7% Open table in a new tab This study showed that uptakes on FDG-PET tended to be higher-intensity, well-defined and varied within an early period after SRT, and to be lower-intensity and ill-defined in a late period. That would help interpretation of FDG-PET for follow-up of cases treated with SRT.

1427 POSTER Fractionated stereotactic radiation therapy using cyberknife for primary liver cancer

Stereotactic radiotherapy (SRT) of brain metastases is considered effective when long-term local control is obtained. However, dose–effect data are scarce. We, therefore, performed a systematic literature search to assess the evidence concerning the relation of SRT dose and local control probability.A search was performed for papers describing patients treated with SRT for brain metastases, published from 1990 through 2009, in the electronic databases Medline (Pubmed) and Embase. We selected only papers reporting actuarial local control probability, in which a fixed dose had been prescribed and in which the size of the metastases was given. Series with SRT as a boost after whole brain irradiation (WBI) or with SRT after surgery were excluded. From the selected papers we extracted data on dose, local control rates and necrosis rates. Biological effective doses of the linear-quadratic-cubic model, using an α/β of 12 Gy (BED12), were calculated and a dose–response curve was constructed.Eleven papers fulfilled the selection criteria for further analysis. Six-month local control rates were higher than 80% in almost all the series irrespective of dose. Twelve-month local control rates, however, varied and were higher than 80%, higher than 60% and lower than 50% with single doses of ⩾21 Gy, ⩾18 Gy and ⩽15 Gy, respectively, and 70% or higher with fractionated SRT (FSRT). A BED12 of at least 40 Gy was associated with a twelve–month local control rate of 70% or more.Local control after single fraction SRT is highly dependent upon dose and is high (>80%) after 21 Gy or more, but low (<50%) after 15 Gy or less. We conclude that SRT for brain metastases should preferably be applied with a BED12 of at least 40 Gy corresponding with a single fraction of 20 Gy, two fractions of 11.6 Gy or three fractions of 8.5 Gy.

Preliminary results of a phase I study of stereotactic radiotherapy for unresectable primary and metastatic liver cancer

4127 Purpose: To report initial toxicity and response data from a phase I study of stereotactic radiotherapy (SRT) for unresectable liver cancer. Methods: Eligible patients have unresectable or medically inoperable primary or metastatic liver cancer, Childs score A and KPS ≥ 60. Standard treatment options have been explored. Patients are stratified based on diagnosis (metastases vs. primary cancer) and volume of uninvolved liver treated (< 20%, 20–50%, 50–80%). SRT is delivered in 6 fractions/2 weeks to maximize patient convenience, resource utilization and therapeutic gain. Dose is individualized to maintain the same estimated risk of liver toxicity for patients at each level (level I - 5% risk, level II - 10% risk, level III - 20%, max. dose 60 Gy in 6 fractions). Escalation to level II and III occurs once at least 3 patients have been followed for >3 months without dose limiting toxicity for each stratum at the previous level. Patients are treated during breath hold to reduce organ motion, with daily imaging and repositioning to reduce setup error. Acute toxicity scored using CTC v3.0. Results: From Aug 2003 to Dec 2004, 36 patients completed SRT at levels I and II (14 hepatocellular carcinoma, 6 cholangiocarcinoma, 16 metastases). The median tumor volume was 213.9 cm3 (range 9.2 to 3088cm3). The average SRT dose to tumor was 35.7 Gy (range: 24 to 56.3 Gy). Median follow-up was 5.5 months (1.4 to 14.9 months). No grade 4/5 related toxicity was seen. At 1 month, 4 patients with HCC had a decline in liver function to Child B. No radiation-induced liver disease (RILD) was observed. Toxicity within 3 months included: grade 3 fatigue (1), vomiting (1); grade 2: thrombocytopenia (2), gastritis (4), pruritis (2), vomiting (2), nausea (6), anorexia (2) fatigue (8), hepatic pain (2). One gastrointestinal bleed occurred 6.4 months following SRT in a patient with tumor extension to the stomach on endoscopy. In 28 evaluable patients, in-field response assessed using CT at 3 months was: CR (1), PR (9), MR/SD (14), PD (4) Conclusion: This approach of individualized dose SRT appears safe, with no severe liver toxicity observed to date. More patients and longer follow up are required for a further assessment of late toxicity and efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ASCO CDA, Canadian Institutes of Health Research, NIH (US)/ NCI, NIH (US)/ Ontario portion/year, Ontario Cancer Research Network, Lustgarten Foundation for Pancreatic Cancer Research

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

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). 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%). 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). 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.