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Title: TU-H-BRC-02: Biological Dose Escalation for Liver SBRT Through Spatiotemporal Fractionation

Abstract

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulative BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number ofmore » fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

Authors:
; ; ;  [1]
  1. Massachusetts General Hospital, Boston, MA (United States)
Publication Date:
OSTI Identifier:
22654017
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; FRACTIONATED IRRADIATION; LIVER; NEOPLASMS; RADIATION DOSE DISTRIBUTIONS; RADIOTHERAPY; X RADIATION

Citation Formats

Unkelbach, J, Perko, Z, Wolfgang, J, and Hong, T. TU-H-BRC-02: Biological Dose Escalation for Liver SBRT Through Spatiotemporal Fractionation. United States: N. p., 2016. Web. doi:10.1118/1.4957609.
Unkelbach, J, Perko, Z, Wolfgang, J, & Hong, T. TU-H-BRC-02: Biological Dose Escalation for Liver SBRT Through Spatiotemporal Fractionation. United States. doi:10.1118/1.4957609.
Unkelbach, J, Perko, Z, Wolfgang, J, and Hong, T. 2016. "TU-H-BRC-02: Biological Dose Escalation for Liver SBRT Through Spatiotemporal Fractionation". United States. doi:10.1118/1.4957609.
@article{osti_22654017,
title = {TU-H-BRC-02: Biological Dose Escalation for Liver SBRT Through Spatiotemporal Fractionation},
author = {Unkelbach, J and Perko, Z and Wolfgang, J and Hong, T},
abstractNote = {Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulative BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.},
doi = {10.1118/1.4957609},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = 2016,
month = 6
}
  • Purpose: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for lung metastases. Methods and Materials: A Phase I clinical trial was conducted. Eligible patients had one to three pulmonary metastases from a solid tumor, cumulative tumor diameter <7 cm, and adequate pulmonary function (forced expiratory volume in 1 s {>=}1.0 L). The planning target volume (PTV) was typically constructed from the gross tumor volume (GTV) by adding a 5-mm radial and 10-mm craniocaudal margin. The first cohort received 48 Gy to the PTV in three fractions (F). SBRT dose was escalated in subsequent cohorts upmore » to a preselected maximum of 60 Gy/3 F. The percent of normal lung receiving more than 15 Gy (V{sub 15}) was restricted to less than 35%. Respiratory control and a dynamic conformal arc SBRT technique were used. Dose-limiting toxicity (DLT) included acute Grade 3 lung or esophageal toxicity or any acute Grade 4 toxicity within 3 months. After the Phase I dose escalation, the trial continued as a Phase II study, and patients in this cohort are included to increase the number of patients evaluable for early toxicity assessment. Results: Twenty-five eligible patients have been enrolled to date. In the Phase I component of the trial, there were 12 patients (7 male, 5 female): median age, 55 years (range, 31-83 years); the most common primary site was colorectal (4 patients). Seven patients had two lung lesions, and 1 patient had three lesions. The median aggregate volume of all GTVs was 18.7 mL (range, 2-40 mL). No patient experienced a DLT, and dose was escalated to 60 Gy/3 F without reaching the MTD; including the additional Phase II cohort patients, 16 patients have been treated to a dose of 60 Gy/3F without experiencing a DLT in the first 3 months. The equivalent uniform dose to the GTV in the highest dose group ranged from 66 to 77 Gy in 3 F. Conclusions: In patients with limited pulmonary metastases, radiobiologically potent doses of SBRT are well tolerated with minimal early toxicity. A Phase II SBRT study of 60 Gy/3 F for lung metastases is ongoing to evaluate local tumor control rates with this regimen and continue surveillance for any late effects.« less
  • Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescriptionmore » adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas SBRT treatment planning. Further investigations with a larger number of patients are necessary. The project is partially supported by Philips Medical Systems.« less
  • Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by usingmore » Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.« less
  • Purpose: We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Between February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions. Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas. The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy. Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing riskmore » of death. Results: All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity. Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed. After a median of 17 months follow-up (range, 2-55 months), the cumulative risk of LF at 12 months was 23%. Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died. The median survival was 28.6 months, and the 2-year actuarial overall survival was 50.4%. Conclusions: It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring {<=}5 cm. Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity. Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life.« less
  • Purpose: Stereotactic body radiotherapy (SBRT) combining transarterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study aims to evaluate the impact of Lipiodol on dose distribution by comparing the dosimetric performance of the Acuros XB (AXB) algorithm, anisotropic analytical algorithm (AAA), and Monte Carlo (MC) method using a virtual heterogeneous phantom and a treatment plan for liver SBRT after TACE. Methods: The dose distributions calculated using AAA and AXB algorithm, both in Eclipse (ver. 11; Varian Medical Systems, Palo Alto, CA), and EGSnrc-MC were compared. First, the inhomogeneity correction accuracy of the AXB algorithm and AAA wasmore » evaluated by comparing the percent depth dose (PDD) obtained from the algorithms with that from the MC calculations using a virtual inhomogeneity phantom, which included water and Lipiodol. Second, the dose distribution of a liver SBRT patient treatment plan was compared between the calculation algorithms. Results In the virtual phantom, compared with the MC calculations, AAA underestimated the doses just before and in the Lipiodol region by 5.1% and 9.5%, respectively, and overestimated the doses behind the region by 6.0%. Furthermore, compared with the MC calculations, the AXB algorithm underestimated the doses just before and in the Lipiodol region by 4.5% and 10.5%, respectively, and overestimated the doses behind the region by 4.2%. In the SBRT plan, the AAA and AXB algorithm underestimated the maximum doses in the Lipiodol region by 9.0% in comparison with the MC calculations. In clinical cases, the dose enhancement in the Lipiodol region can approximately 10% increases in tumor dose without increase of dose to normal tissue. Conclusion: The MC method demonstrated a larger increase in the dose in the Lipiodol region than the AAA and AXB algorithm. Notably, dose enhancement were observed in the tumor area; this may lead to a clinical benefit.« less