Normal Liver Volume Research Articles

SU‐E‐P‐52: Dose‐Volume Toxicity Analysis of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Purpose:To investigate the relationship between physical and biological effective dose (BED) to liver toxicity for SBRT fractionations.Methods:A total of 16 patients (13–10×3Gy, 2–5×10Gy and 1–3×15Gy were selected. Physical dose distributions were converted to voxel based BED values using the linear‐quadratic (LQ) and linear‐quadratic linear (LQ‐L) models for doses per fraction larger than 6Gy. Patients were graded for effective toxicity (post‐treatment minus pre‐treatment grades) using the RTOG Late Radiation Morbidity Scoring Schema associated with Radiation Induced Liver Disease (RILD). Evaluated physical dose‐volume levels consisted of V10Gy, V15Gy, V20Gy, V25Gy and V30Gy which were then converted to BED values corresponding to V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3, respectively. All levels were normalized to their respective patient normal liver volumes (NLV) and evaluated for correlation to RILD. Results were measured quantitatively using R‐squared regression analysis.Results:Mean Dose Tolerable to Normal Liver (MDTNL) against RILD grade resulted in an R‐squared value of 0.0104. NLV‐normalized physical dose linear regression fit of V10Gy, V15Gy, V20Gy, V25Gy and V30Gy against RILD yielded R‐squared values of 0.1041, 0.0895, 0.0698, 0.0398 and 0.0009 while BED levels of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in values of 0.0002, 0.0153, 0.0533, 0.0427 and 0.0072, respectively. The average NLV‐normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy per grade plotted against RILD grade yielded R‐squared correlations of 0.8092, 0.6362, 0.5899, 0.5846 and 0.0224 while the BED levels of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in R‐squared correlations of 0.0003, 0.3831, 0.8476, 0.678 and 0.076, respectively.Conclusion:Regression analysis between physical dose, BED and RILD showed strong correlation for the V30Gy and V46.7Gy3 dose‐levels. Average BED and physical dose per grade both exhibit strong correlations to RILD however, a lack of statistical significance exists due to small patient sample size.

SU‐F‐BRB‐04: Comparison of Coplanar VMAT, Non‐Coplanar VMAT, and 4π Treatment Plans

Purpose:The 4π non‐coplanar radiotherapy delivery technique has demonstrated significantly better normal tissue sparing and dose conformality than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The non‐coplanar basis of 4π is incorporated into VMAT treatment planning to compare its effect on plan quality.Methods:Clinical stereotactic body radiation therapy plans for 9 liver patients treated with 30–60 Gy using coplanar VMAT (cVMAT) were re‐planned using non‐coplanar VMAT (nVMAT) with 3 arcs and 4 π with 20 intensity‐modulated non‐coplanar fields. All plans were optimized to deliver 100% of the prescribed dose to 95% of the planning target volume (PTV), and nVMAT and 4π plans were tailored to match the maximum and mean PTV dose from the clinical plan. The conformality index (CI), 50% dose spillage volume (R50), normal liver volume receiving >15 Gy (VL>15), and doses to organs at risk (OARs) were compared for all three treatment plans.Results:Compared to cVMAT, the nVMAT and 4π plans reduced VL>15 by an average of 30.6 cm3 and 96.3 cm3, respectively. The average CI was also reduced from 1.22 (cVMAT) to 1.17 (nVMAT) and 1.14 (4π), indicating higher conformality in the same order. Similarly, R50 was reduced from 3.87 (cVMAT) to 3.58 (nVMAT) and 2.74 (4π). With the exception of the mean right kidney dose, which increased by an average of only 0.6 Gy for nVMAT, the dose differences to OARs were not statistically significant between the two VMAT plans. 4π plans either significantly decreased or maintained OAR doses.Conclusion:While the manual selection of intuitive non‐coplanar arcs does show some improvement over coplanar VMAT, the automated beam selection for 4π still results in superior plan quality.This project is supported in part by Varian Medical Systems and NIH R43 CA183390.

Risk factors for hepatitis B virus reactivation after conformal radiotherapy in patients with hepatocellular carcinoma

This study investigated whether conformal radiotherapy affects hepatitis B virus (HBV) reactivation, and the risk factors for HBV reactivation in patients with HBV-related hepatocellular carcinoma (HCC). Sixty-nine patients with HCC were included in this retrospective study. Before radiotherapy (RT), all patients underwent imaging examinations and some baseline examinations, including CBC, liver function test, renal function test, α-fetoprotein level, hepatitis B (HB) surface antigen, HB surface Ab, HB e antigen, HB e Ab, and serum HBV DNA quantification. During the period of RT and at least 16 weeks after the end of RT, CBCs were carried out weekly and the other tests were monitored monthly or more frequently if necessary. The clinical features and dosimetric parameters of RT were recorded. Univariate and multivariate logistic regression algorithms were used to analyze the risk factors of HBV reactivation. The incidence of complications in the study population was as follows: radiation-induced liver disease, 17.4%; HBV reactivation, 24.6%; and HBV reactivation-induced hepatitis, 21.7%. The HBV DNA level and dose volume parameters including normal liver volume, V20, and mean dose were associated with HBV reactivation. There was a relatively high incidence of HBV reactivation in HCC patients after the end of conformal RT. The serum HBV DNA level and some dosimetric parameters related to normal liver, including normal liver volume, V20, and mean dose, were the prognosis factors of HBV reactivation and should be carefully considered before conformal RT.

A comparison of liver protection among 3-D conformal radiotherapy, intensity-modulated radiotherapy and RapidArc for hepatocellular carcinoma

PurposeThe analysis was designed to compare dosimetric parameters among 3-D conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) and RapidArc (RA) to identify which can achieve the lowest risk of radiation-induced liver disease (RILD) for hepatocellular carcinoma (HCC).MethodsTwenty patients with HCC were enrolled in this study. Dosimetric values for 3DCRT, IMRT, and RA were calculated for total dose of 50 Gy/25f. The percentage of the normal liver volume receiving >40, >30, >20, >10, and >5 Gy (V40, V30, V20, V10 and V5) were evaluated to determine liver toxicity. V5, V10, V20, V30 and Dmean of liver were compared as predicting parameters for RILD. Other parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V110%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (Dmean) for the organs at risk (OARs) and the maximal dose at 1% volume (D1%) for the spinal cord.ResultsThe Dmean of IMRT was higher than 3DCRT (p = 0.045). For V5, there was a significant difference: RA > IMRT >3DCRT (p <0.05). 3DCRT had a lower V10 and higher V20, V30 values for liver than RA (p <0.05). RA and IMRT achieved significantly better CI and lower V110% values than 3DCRT (p <0.05). RA had better HI, lower MUs and shorter delivery time than 3DCRT or IMRT (p <0.05).ConclusionFor right lobe tumors, RapidArc may have the lowest risk of RILD with the lowest V20 and V30 compared with 3DCRT or IMRT. For diameters of tumors >8 cm in our study, the value of Dmean for 3DCRT was lower than IMRT or RapidArc. This may indicate that 3DCRT is more suitable for larger tumors.

Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters

BackgroundTo investigate the clinical and dose–volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).MethodsBetween March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10–20 Gy (median, 15 Gy) per fraction was given over 3–4 consecutive days for a total dose of 30–60 Gy (median, 45 Gy). The following clinical and dose–volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy).ResultsSeventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in ≥ grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose–volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD.ConclusionsThe Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed.

Comparison of dosiology between three dimensional conformal and intensity-modulated radiotherapies (5 and 7 fields) in gastric cancer post-surgery

The purpose of this study was to compare the dose distribution of intensity-modulated radiotherapy (IMRT) in 7 and 5 fields as well as 3-D conformal radiotherapy (3D-CRT) plans for gastric cancer using dosimetric analysis. In 15 patients with gastric cancer after D1 resection, dosimetric parameters for IMRT (7 and 5 fields) and 3D-CRT were calculated with a total dose of 45 Gy (1.8 Gy/day). These parameters included the conformal index (CI), homogeneity index (HI), maximum dose spot for the planned target volume (PTV), dose-volume histogram (DVH) and dose distribution in the organs at risk (OAR), mean dose (Dmean), maximal dose (Dmax) in the spinal cord, percentage of the normal liver volume receiving more than 30 Gy (V30) and percentage of the normal kidney volume receiving more than 20 Gy (V20). IMRT (7 and 5 fields) and 3D-CRT achieved the PTV coverage. However, IMRT presented significantly higher CI and HI values and lower maximum dose spot distribution than 3D-CRT (P=0.001). For dose distribution of OAR, IMRT had a significantly lower Dmean and Dmax in spinal cord than 3D-CRT (P=0.009). There was no obvious difference in V30 of liver and V20 of kidney between IMRT and 3D-CRT, but 5-field IMRT showed lower Dmean in the normal liver than other two plans (P=0.001). IMRT revealed favorable tumor coverage as compared to 3D-CRT and IMRT plans. Specifically, 5-field IMRT plan was superior to 3D-CRT in protecting the spinal cord and liver, but this superiority was not observed in the kidney. Further studies are needed to compare differences among the three approaches.

Multi-institutional comparison of treatment planning using stereotactic ablative body radiotherapy for hepatocellular carcinoma – benchmark for a prospective multi-institutional study

IntroductionSeveral single institution phase I and phase II trials of stereotactic ablative body radiotherapy (SABR) for liver tumors have reported promising results and high local control rates of over 90%. However, there are wide variations in dose and fractionation due to different prescription policies and treatment methods across SABR series that have been published to date.This study aims to assess and minimize inter-institutional variations in treatment planning using SABR for hepatocellular carcinoma (HCC) in preparation for a prospective multi-institutional study.MethodsFour institutions (A-D) participated in this study. Each institution was provided with data from four cases, including planning and diagnostic CT images and clinical information, and asked to implement three plans (a practice plan and protocol plans 1 and 2). Practice plans were established based on the current treatment protocols at each institution. In protocol plan 1, each institution was instructed to prescribe 40 Gy in five fractions within 95% of the planning target volume (PTV). After protocol plan 1 was evaluated, we made protocol plan 2, The additional regulation to protocol plan 1 was that 40 Gy in five fractions was prescribed to a 70% isodose line of the global maximum dose within the PTV. Planning methods and dose volume histograms (DVHs) including the median PTV D50 (Dm50) and the median normal liver volume that received 20 Gy or higher (Vm20) were compared.ResultsIn the practice plan, Dm50 was 48.4 Gy (range, 43.6-51.2 Gy). Vm20 was 15.9% (range, 12.2-18.9%). In protocol plan 1, the Dm50 at institution A was higher (51.2 Gy) than the other institutions (42.0-42.2 Gy) due to differences in dose specifications. In protocol plan 2, variations in DVHs were reduced. The Dm50 was 51.9 Gy (range, 51.0-53.1 Gy), and the Vm20 was 12.3% (range, 10.4-13.2%). The homogeneity index was nearly equivalent at all institutions.ConclusionsThere were notable inter-institutional differences in practice planning using SABR to treat HCC. The range of PTV and normal liver DVH values was reduced when the dose was prescribed to an isodose line within the PTV. In multi-institutional studies, detailed dose specifications based on collaboration are necessary.

Radiotherapy for Hepatocellular Carcinoma With Tumor Vascular Thrombus: Ready for Prime Time?

Radiotherapy for Hepatocellular Carcinoma With Tumor Vascular Thrombus: Ready for Prime Time?

Proton therapy for hepatocellular carcinoma.

Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of HCC.

Stereotactic radiotherapy (SRT) for primary and metastatic liver tumors with functional treatment planning.

222 Background: We report on outcomes and toxicity of liver SRT/SBRT based on 3D-CT/SPECT treatment planning with conformal avoidance of well perfused functional normal liver volumes (FNLV). Methods: 51 patients with unresectable metastatic (36) or primary (15) hepatic tumors (65 targets) completed SRT planning with 99mTc sulfur colloid 3D-SPECT/CT to define FNLVs. Various degrees of FNLV retraction as a result of hepatic cirrhosis or systemic or intrahepatic chemotherapy were observed. For conformal avoidance of the residual FNLV, total dose and fractionation were adapted to FNLV constraints. 4D-CT and SPECT-based dosimetry were compared and treatment outcomes and toxicity were analyzed with medium followup 14.5 months (3-36months). Results: The in-field local control rate was 95%, hepatic failure free survival - 88%, hepatic progression free survival - 78% and overall survival - 70%. 25% patients developed Grade ≤ 2 elevation of liver enzymes with no incidence of “classic” radiation-induced liver disease. No patients with hepatic cirrhosis had Child-Pugh score progression. The most common toxicity was Grade ≤ 2 fatigue. For the group, FNLVs were significantly reduced compared to CT-derived NLV (p&lt;0.01) with marked FNLV contraction in patients with Child-Pugh ≥ B cirrhosis, those who completed hepatic resections or received TACE within 2 months prior to SRT. Treatment planning with incorporated SPECT/CT helps to reduce volumes of functionally active liver parenchyma receiving doses above prescription threshold in patients with HCC compared to conventional 4D-CT treatment planning (p&lt;0.01). There was no such correlation for non-HCC patients. Conclusions: 3D-SPECT/CT treatment planning allows identification and conformal avoidance of FNLV from high radiation doses facilitating safety of liver SRT in patients with preexisting liver disease. Outcomes are favorable, however participation in prospective Phase III trial would estimate true value of this method.

Peripheral platelet count correlates with liver atrophy and predicts long-term mortality on the liver transplant waiting list

Several studies have shown a direct role of liver atrophy in the pathogenesis of thrombocytopenia of cirrhosis via reduced production of thrombopoeitin. About 181 patients listed for liver transplantation at a single transplant center were evaluated at the time of listing with laboratory tests and volumetric liver measurements using computed tomography. Expected normal liver volume was calculated using the Heinemann formula. Liver volume ratio (LVR) was calculated as actual liver volume over expected liver volume. Patients were predominantly male (70.7%), with viral hepatitis (60.2%), had a mean age of 51.8 years (SD 8.7), model for end stage liver disease (MELD) of 14 (SD 6.4), LVR of 0.95 (SD 0.3), and platelet count of 105,000/mcL (SD 66,000). Platelet count (P < 0.0001) correlated more strongly with LVR than MELD, MELD components (P = 0.27) or serum albumin (P = 0.003). Platelet count (HR 0.987, 95% CI 0.979-0.994, P = 0.001) was a strong independent predictor of mortality. Patients with platelet count < 100,000/mcL had a shorter survival (935 vs. 1396 days, P = 0.002) and higher death rate (42.2% vs. 23.6%, P = 0.01), but no different transplantation rate (36.7% vs. 33.3%, P = 0.64) compared to those with platelet count ≥ 100,000/mcL. Low platelet count corresponds to higher waiting list mortality and is a sign of advanced liver atrophy.

Robotic Radiosurgery for Liver Metastases

Purpose: The prevalence of liver metastases is very high for patients whose primary diagnosis are colorectal, pancreas, lung, and breast cancer. Local control of the disease may increase both quality of life and survival. The aim of this study to show feasibility, efficiency, and low morbidity combined with a high local control probability in use of robotic stereotactic body radiation therapy (rSBRT) treatment for liver metastases. Methods and Materials: A total of 55 patients with 84 liver metastases from different primary sites who underwent rSBRT in our center between July 2006 and December 2011 were reviewed for this study. Patients who refused surgery or judged inoperable were included in this study. Patients were required to have adequate liver function and more than three months minimum life expectancy. An average of three (3-5) fiducial markers were implanted percutaneously under CT-guidance with local anaesthesia. Maximum three liver metastases from any primary sites were treated and accepted for this study. Treatment planning CT, magnetic resonance imaging (MRI), and positron emission tomography-CT (PET-CT) were used for tumor delination. Treatment plan dose was prescribed at the PTV with an isodose line range 70-85% which was covering the 95% volume of PTV. We mandated that minumum 700 cc of normal liver had to receive at total dose less than 15 Gy in three to five fractions. The patients were examined every three months after rSBRT by biochemical examinations and imaging. PET-CT or MRI were performed at each follow-up. Results: Fifty-five patients (32 males, 23 females) who had liver metastases from various primary sites were treated with rSBRT using real-time tumor tracking system. Mean age of patients was 61 years (range 22 to 86 years). The primary sites included colorectal (n=23), pancreas (n=8), breast (n=7), lung (n=6), bladder (n=3), and others (n=8). The total prescribed dose was 45 Gy (range 24 Gy to 45 Gy) in median 3 (range three to six) fractions. The minimum normal liver volume (700 cc) was received mean 7.8 Gy (range 2 Gy to 14.6 Gy). Forty-nine (89%) patients were evaluated for tumor response, local control and survival analysis. The median follow-up was 12 months (range four to 39 months). CR was seen in 25 (51%) patients, PR in 12 (25%) patients, and SD in two (4%) patients at first follow-up. Ten (10%) patients had progressed inside the treated volume at first follow-up. The actuarial local control rate for patients is shown in Figure 2. The actuarial one-year and two-year local control rates were 61% (95% confidence interval (CI), 53%-69%) and 39% (95% CI, 28%-49%), respectively. The median overall survival was 16 months. The actuarial one-year and two-year overall survival rates were 79% (95% (CI), 73%-85%) and 56% (95% CI, 48%-63%), respectively. Conclusion: The results of our study have show that rSBRT for the treatment of liver metastases is feasible and safe with minimal side-effects. Further studies are required with larger patient series to compare rSBRT with other local ablative techniques and systemic therapies.

Proton therapy for hepatocellular carcinoma

Proton radiotherapy has seen an increasing role in the treatment of hepatocellular carcinoma (HCC). Historically, external beam radiotherapy has played a very limited role in HCC due to a high incidence of toxicity to surrounding normal structures. The ability to deliver a high dose of radiation to the tumor is a key factor in improving outcomes in HCC. Advances in photon radiotherapy have improved dose conformity and allowed dose escalation to the tumor. However, despite these advances there is still a large volume of normal liver that receives a considerable radiation dose during treatment. Proton beams do not have an exit dose along the beam path once they enter the body. The inherent physical attributes of proton radiotherapy offer a way to maximize tumor control via dose escalation while avoiding excessive radiation to the remaining liver, thus increasing biological effectiveness. In this review we discuss the physical attributes and rationale for proton radiotherapy in HCC. We also review recent literature regarding clinical outcomes of using proton radiotherapy for the treatment of HCC.

4π Non-Coplanar Liver SBRT: A Novel Delivery Technique

To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving <15 Gy, integral dose, and 50% dose spillage volumes were compared against the delivered clinical VMAT plans. Compared with the VMAT plans, the 4π plans yielded reduced 50% dose spillage volume and integral dose by 22% (range 10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume receiving <15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of the mean normal liver dose. Mean doses to the left kidney and right kidney and maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%, 67%, and 64% (P≤.05). This novel 4π non-coplanar radiation delivery technique significantly improved dose gradient, reduced high dose spillage, and improved organ at risk sparing compared with state of the art VMAT plans.

Tolerance of Cirrhotic Liver Comparing With Normal Liver to Stereotactic Body Radiation Therapy

Purpose/Objective(s): In recent years stereotactic body radiation therapy (SBRT) has been used to treat liver cancer and has resulted in good outcomes. However, the hepatic tolerance to small volume with hypofractionated high dose irradiation is unclear. Especially partial liver irradiation to high doses may render cirrhotic liver more susceptible to RT-induced liver injury than normal liver. We investigated and analyzed the hepatic radiation injury associated with the dose distribution by using MRI with hepatocyte-targeted Gd-EOB-DTPA. Materials/Methods: A total of 19 liver cancer patients were treated by SBRT. Of these patients, 13 were hepatocellular carcinoma (HCC) in liver cirrhosis, and 6 were metastatic cancer in normal liver. The median prescribed dose delivered to the PTV was 52 Gy (range, 40-56 Gy), with median fraction size of 9 Gy (range, 5-14 Gy) and in a median total irradiation time of 6 days (range, 4-12 days). MRI was performed during 3-6 months after SBRT. MR-sequences were conducted with T1WI with GRE (LAVA; liver acquisition with volume acceleration) enhanced by Gd-EOB-DTPA. All MRI data sets were merged with 3D-dosimetry data by using in-house DICOM-RT image fusion software. The reviewer indicated the border of hypointensity on T1WI (loss of hepatocyte function) and read the isodose line on the border. This boundary doses were corrected to biologically effective dose (BED) using the linear-quadratic (LQ) formulation assuming an a/ b Z 2 Gy for intercomparing over a wide variety of dose distribution around the border. Results: The registration errors were negligible small after image fusion of the planning CT to the follow-up MRI so that the development of hepatocyte dysfunction was definitely validated in correlation to the isodose distribution. The dose per fraction at the border of hepatocyte dysfunction was a median of 4 Gy (range, 2.4-8 Gy). This results indicated that the minimal BED provoking hepatocyte function loss was a median of 105 Gy (range, 70-137 Gy, using LQ formulation, a/b Z 2 Gy) in normal liver. However, in cirrhotic liver, it was significantly decreased to a median of 51 Gy (range, 30-70 Gy, using LQ formulation, a/b Z 2 Gy) so that the toxic effects lowered the threshold dose for hepatic dysfunction in liver cirrhosis. Conclusions: For liver SBRT, the fundamental premise is that to preserve adequate liver function, a minimum volume of normal liver must be spared from receiving a dose that might render it nonfunctional. In this study, the maximum dose allowed to this critical volume was estimated to be 16 Gy in four fractions (BED Z 50 Gy based on LQ conversion, a/b Z 2 Gy) in cirrhotic liver which was half of the BED for normal liver. Author Disclosure: R. Oh: None. H. Shiomi: None. Y. Imai: None. T. Igura: None. Y. Miyata: None. H. Nakamura: None. T. Inoue: None.

Outcomes of Stereotactic Radiation Therapy (SRT) for Primary and Metastatic Liver Tumors with 3-D CT and Single Photon Emission Computed Tomography (3D-CT/SPECT) Treatment Planning

SPECT provides functional imaging of the liver parenchyma through the uptake of radioactive colloid by Kupffer cells in proportion to vascular perfusion. We report on outcomes and toxicity of liver SRT/SBRT based on 3D-CT/SPECT treatment planning with conformal avoidance of well-perfused functional normal liver volumes (FNLV).

TH‐A‐213AB‐07: Beam Orientation Optimization in 4pi Space for Liver SBRT

Purpose: Non‐coplanar beam geometry has been shown to improve plan conformity but manual selection of non‐coplanar beams is difficult. Previous beam orientation optimization algorithms did not include dose distribution explicitly in the objective function. Therefore, their ability to achieve high quality plans efficiently and automatically was limited. The purpose of this study is to implement a novel non‐coplanar 4pi optimization algorithm that overcomes these difficulties. Methods: A two stage inverse optimization was performed to select the beams and optimize fluences. For both stages, a pricing and column generation algorithm was used to iteratively optimize the inner product of the derivative of the objective function and the beam or beam aperture. The iterative procedure continued until a certain number of beams or beam apertures are selected or until the incremental inner product becomes negative. Ten liver stereotactic body radiation therapy (SBRT) patients previously treated with volumetric modulated arc therapy (VMAT) were replanned using the 4pi technique and compared with the actual delivered plan. 14 noncoplanar fields were selected by the 4pi algorithm to cover 95% of the PTV with the prescription dose. Results: With the same number of beams, the objective function value and the 50% isodose volume (V50) of the 4pi plan converge to a lesser value than the coplanar plan. For the liver cases, an average reduction of 14% in V50 was observed. The average liver dose and the volume of normal liver receiving 15 Gy or higher were reduced for 14% and 19%, respectively. Improved OAR sparing and target dose homogeneity were achieved simultaneously. Greater dosimetric gains were observed on lesions off patient center axis. Conclusions: Significantly improved dosimetry was achieved using the novel 4pi planning method compared with state‐of‐the‐art coplanar technique. 4pi technique is well suited for liver SBRT due to the organ laterality.

SU‐C‐BRB‐04: Isotoxic Hypofractionation for Liver Cancer Radiobiologically Optimized Schedules and Normal Tissue DVH Metrics for NTCP

Purpose: To investigate optimal fractionations to achieve high tumor control probabilities (TCPs) while maintaining acceptable normal‐tissue complication probability (NTCP) using radiobiological models with new parameters derived from recent clinical data for hypofractionated liver‐ cancer patients. Methods and Materials: Biological parameters for the Marsden TCP model were derived from reported outcomes of a multi‐ institutional Phase I/II trial. TCP and NTCP (using the LKB model with Dawson's parameters) were calculated for 8 liver cancer patients treated with different hypofractionation regimens. The correlation between tumor size, the normal liver volume receiving at least 15 Gy and NTCP were examined. Using the BioSuite software, we determined the range of fractionation regimens that achieve high TCP for 5% NTCP. Results: The TCP parameters for liver tumors are: alpha= 0.217 Gy‐1, alpha spread is 0.067 Gy‐1, assuming alpha/beta = 10 Gy and 107 tumor clonogens cm‐3. For any given fractionation we have found that NTCP is not correlated with the absolute liver volume receiving at least 15Gy, nor with the dose received by the hottest 700‐cc of the normal liver; these constraints are widely used in liver hypofractionation treatment planning. Instead, the parameter which correlates best with NTCP is the percentage liver volume receiving at least 15Gy. For 5 of the 8 patients, no more than 3 fractions were required to achieve a TCP over 96%; for 2 patients TCP increased gradually with number of fractions (from 3 to 10) to 95.2% and 92.2% respectively. The remaining patient had a small liver and larger target volume which resulted in high NTCP for any fractionation. Conclusions: A range of different hypofractionated regimens from 3×12Gy to 5×12 Gy is found to ensure excellent outcomes. However, the commonly used dose‐volume metrics for normal liver do not correlate well with NTCP. A new metric is proposed in this study.

Fluorodeoxyglucose Positron Emission Tomography Response and Normal Tissue Regeneration After Stereotactic Body Radiotherapy to Liver Metastases

To characterize changes in standardized uptake value (SUV) in positron emission tomography (PET) scans and determine the pace of normal tissue regeneration after stereotactic body radiation therapy (SBRT) for solid tumor liver metastases. We reviewed records of patients with liver metastases treated with SBRT to ≥40 Gy in 3-5 fractions. Evaluable patients had pretreatment PET and ≥1 post-treatment PET. Each PET/CT scan was fused to the planning computed tomography (CT) scan. The maximum SUV (SUV(max)) for each lesion and the total liver volume were measured on each PET/CT scan. Maximum SUV levels before and after SBRT were recorded. Twenty-seven patients with 35 treated liver lesions were studied. The median follow-up was 15.7 months (range, 1.5-38.4 mo), with 5 PET scans per patient (range, 2-14). Exponential decay curve fitting (r=0.97) showed that SUV(max) declined to a plateau of 3.1 for controlled lesions at 5 months after SBRT. The estimated SUV(max) decay half-time was 2.0 months. The SUV(max) in controlled lesions fluctuated up to 4.2 during follow-up and later declined; this level is close to 2 standard deviations above the mean normal liver SUV(max) (4.01). A failure cutoff of SUV(max) ≥6 is twice the calculated plateau SUV(max) of controlled lesions. Parenchymal liver volume decreased by 20% at 3-6 months and regenerated to a new baseline level approximately 10% below the pretreatment level at 12 months. Maximum SUV decreases over the first months after SBRT to plateau at 3.1, similar to the median SUV(max) of normal livers. Transient moderate increases in SUV(max) may be observed after SBRT. We propose a cutoff SUV(max) ≥6, twice the baseline normal liver SUV(max), to score local failure by PET criteria. Post-SBRT values between 4 and 6 would be suspicious for local tumor persistence or recurrence. The volume of normal liver reached nadir 3-6 months after SBRT and regenerated within the next 6 months.

Assessing Hepatomegaly: Automated Volumetric Analysis of the Liver

The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly. Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated. The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences (P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 ± 0.25 and 2.32 ± 0.75 L, respectively. One-way analysis of variance found that body surface area (P = .004) and gender (P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables (P > .18). H-score cutoffs of 0.92 and 1.08 L/m2 were used to define mild and massive hepatomegaly (95% confidence interval, ± 0.02 L/m2). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98. Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.