Mean Liver Dose Research Articles

Dosimetric analysis of liver toxicity after liver metastasis stereotactic body radiation therapy

PurposeThe aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity. Methods and materialsBetween 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated. Toxicity was defined as grade ≥2 classic or nonclassic radiation induced liver disease (RILD). Specific toxicity endpoints evaluated were worsening transaminases and albumin levels within 3 months of SBRT. ResultsSeventy percent of patients had colorectal carcinoma, 55% had extrahepatic disease, 1 patient had hepatitis B, and 54% had received prior chemotherapy. Baseline transaminases were elevated at Common Terminology Criteria for Adverse Effects, V4.0, grade 1, 2, and 3 levels in 33 (41%), 2 (2%), and 0 (0%) patients. The mean prescription dose was 43 Gy (27.7-60 Gy) in 6 fractions. The mean liver (minus gross tumor volume) dose (MLD) was 16 Gy (3-25.6 Gy) in 6 fractions. No classic or nonclassical ≥grade 2 RILD was observed. Within 3 months of SBRT, 49 (61%) patients had worsening of grade of transaminase and 23 (28%) patients had a reduction in albumin, all transient (majority grade ≤2 toxicity) without subsequent clinical toxicity. Seventeen patients exceeded Quantitative Analysis of Normal Tissue Effects in the Clinic MLD guidelines (≤20 Gy), 13 (76%) of whom had worsening of transaminase grade. On multivariate analysis, worsening of liver enzymes was more likely in patients with higher doses to the spared 700 mL of liver (P = .026), and reduction of albumin was more likely with higher effective liver volume (odds ratio, 1.53 [range, 1.08-2.16]) P = .016). ConclusionsLiver metastases SBRT is safe with a low risk of transient biochemical liver toxicity, more likely in patients with a higher effective liver volume and higher doses to the spared uninvolved liver volume.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: dosimetric comparison and risk assessment of solid secondary cancer.

PurposeTo determine the optimal radiotherapy technique for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), we compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4_field), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT_co) and 7 coplanar and noncoplanar beams (IMRT_non).Materials and MethodsWe retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer.ResultsThe best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4_field, 3D-CRT, IMRT_co, and IMRT_non. On the other hand, the mean liver dose was the highest with 4_field and the lowest with AP/PA. Compared with 4_field, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT_co and IMRT_non increased except the lungs. However, the absolute differences were much lower than <1%.ConclusionTailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).

223 Background: For HCC pts undergoing LT, local regional treatment as a "bridge" is standard to decrease tumor progression. The most common treatment is TACE, but the best bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts planned for accrual. From 9/2014-9/2016, 29 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE pts received 2 treatments one month apart utilizing DEBDOX beads (n = 15). TACE pts were hospitalized after each TACE. Pts receiving SBRT (n = 12) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was time to retreatment of treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. Results: A. Demographics/Toxicity. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears equally effective to TACE as a bridge to liver transplantation, may engender less toxicity, and eliminates hospitalizations. Clinical trial information: NCT02182687. [Table: see text][Table: see text]

Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286cc (range, 766-3967cc), and the median prescribed dose was 36Gy (range, 27-54Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108×109/L vs 150×109/L), higher mean liver dose (OR, 1.33; median, 16.9Gy vs 14.7Gy), and higher dose to 800cc of liver (OR, 1.11; median, 14.3Gy vs 6.0Gy).With 13 CP-B7 patients included or when dose to 800cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900cc) were strongly associated with liver function decline 3months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk.

Defining Radiation-Induced Hepatic Toxicity in Hepatocellular Carcinoma Patients Treated with Stereotactic Body Radiotherapy.

The definition and criteria of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients vary among studies. Therefore, the reported rates of RIHT differ among studies, and this causes confusion. In this study, we evaluated RIHT using several laboratory and clinical parameters, and analyzed which criterion is more correlated with RT and survival. Forty-five HCC patients treated with stereotactic body radiotherapy were included for the analysis. All patients had unresectable HCC and Child-Pugh (CP) class A or B baseline liver function. A median total dose of 45 Gy was delivered by CyberKnife in 3 fractions. For individual laboratory parameter, ≥ grade 2 toxicity development of bilirubin, albumin, or prothrombin time by Common Terminology Criteria of Adverse Effects (CTCAE) was correlated with mean liver dose and survival. However, serum transaminases had no correlation with liver mean dose and survival, and were rather affected by other local treatments. Compared to the CTCAE, the increase in the CP score of 2 points or more was better correlated with liver failure and overall survival, and it was not affected by other local treatments or tumor progression. We concluded RIHT was better defined by the change in the CP score rather than the CTCAE in patients treated by stereotactic body radiotherapy for HCC.

Identification of the suitable leaf margin for liver stereotactic body radiotherapy with flattening filter-free beams

The purpose of this study is to identify the suitable leaf margin for liver stereotactic body radiotherapy (SBRT) with flattening filter-free (FFF) beams, as compared with that with flattening filter (FF) beams. SBRT treatment planning for 10 patients with liver cancer was performed using 10-MV FFF and FF beams obtained from a Varian TrueBeam (Varian Medical Systems, Palo Alto, CA) linear accelerator. Each plan was generated with the leaf margin to the planning target volume (PTV) ranging from −3 to 5 mm. The prescription dose at D95 (dose covering 95% of the volume) was 48 Gy in 4 fractions to the PTV. The following dosimetric parameters were evaluated quantitatively: homogeneity index (HI), conformity index (CI), gradient index (GI), the normal liver receiving a dose greater than or equal to 20 Gy (V20), and the mean normal liver dose. The HI for FFF and FF beams increased as the leaf margin decreased. The leaf margins that achieved the best CI and GI were 0.1 and −0.3 mm for FFF beams, and 0.1 and −0.9 mm for FF beams. The liver V20 and the mean liver dose reached their minimum values at leaf margins of −0.8 and 0.0 mm for FFF beams, and −0.8 and 0.0 mm for FF beams. The suitable leaf margin for SBRT planning did not differ significantly for FFF and FF beams. Our data showed that, for both FFF and FF beams, a leaf margin of 0 or −1 mm was optimal for liver SBRT planning in terms of both target coverage and normal tissue sparing.

SU-F-T-606: Monte Carlo Evaluation of Tissue Inhomogeneity Corrections in the Treatment of Liver Cancer Patients Using Stereotactic Body Radiotherapy

Purpose: To evaluate the dosimetric performance of X-ray Voxel Monte Carlo(XVMC) algorithm in effort to clinically validate Monte Carlo-approach in heterogeneous liver phantom and liver SBRT plans. Methods: An anthropomorphic RPC liver phantom incorporating a liver structure with two cylindrical targets and organs-at-risk (OARs) was used in phantom validation. Subsequently, five patients with metastatic liver cancer were treated using heterogeneity-corrected pencil-beam(PB-hete)algorithm were analyzed following RTOG-1112 criteria .ITV was delineated on MinIP and OARs were contoured on MeanIP images of 4D-CT. PTV was generated from ITV with 5-10mm uniform margin. Mean PTV was 81.3±46.4cc. Prescription was 30–45Gy in 5 fractions, with at least PTV(D95%)=100%. Hybrid SBRT plans were generated with noncoplanar/3D-conformal arcs plus static-beams at Novalis-TX consisting of HD-MLC and 6MV-SRS. SBRT plans were re-computed using XVMC algorithm utilizing identical beam-geometry, MLC-positions, and monitor units and subsequently compared to clinical PB-hete plans. Results: Our results using RPC liver motion phantom validation were all compliance with MD Anderson standards. However, compared to PB-hete, average target volume encompassed by the prescribed percent isodose (Vp) was 9.1% and 8.5% less for PTV1 and PTV2 with XVMC. For the clinical liver SBRT plans, PB-hete systematically overestimated PTV dose (D95, Dmean and D10) within ±2.0% (p<0.05) compared to XVMC. Mean value of Vp was about 3.8% less with XVMC compared to PB-hete (ranged 2.9–5.7% (p<0.003)). However, mean liver dose (MLD) was 3.2% higher (p<0.003), on average, with XVMC compared to clinical PB-hete (ranged −1.0to−3.9%). OARs doses were statistically insignificant. Conclusion: Results from our XVMC dose calculations and validation study for liver SBRT indicate small-to-moderate under-dosing of the tumor volume when compared to PB-hete. Results were consistent with phantom validation and patients plans. However, Vp was less by up to 5.7% for some liver SBRT patients with XVMC–suggesting under-dosing of the target volume and overdosing of MLD by up to 3.9% occurred with PB-hete plan. These differences between PB-hete and XVMC dose calculations may be of clinical interest.

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

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.

SU‐F‐T‐544: Development of a Clinically Feasible Workflow of 4D MRI‐Based Treatment Planning for Liver SBRT

Purpose:To develop a clinically feasible workflow of 4D MRI‐based treatment planning for liver SBRT.Methods:A clinical workflow based on 4D MRI for liver SBRT was designed to largely simulate the same procedure as 4D CT for lung SBRT. Key features of the workflow include: (1) contouring tumor volume at each phases (2) contouring more structures, (3) assigning CT numbers to structures for dose calculation. Uncertainties (bone delineation, MRI distortion, CT number assignment, etc.) were investigated using five clinical treatment plans of liver SBRT by simulating the following scenarios: homogeneous calculation, calculation with CT number assignment (for each structure separately and for all combined), calculation with and without distortion (mimicked by shirking body structure by 1mm to 5 mm). Dose‐histogram volume (DVF) parameters were collected from the simulated cases and compared to those in the original plan. Lastly, a patient example case of 4D MRI‐based treatment plan was performed to demonstrate the feasibility of the proposed workflow.Results:In homogeneous calculation, the average percentage volume error (ΔV30) of liver was 0.40% and maximum average dose error (GTV ΔD95) was 1.08Gy. Between MRI‐based and original plans, liver ΔV30 was 0.28% and maximum average dose error (GTV ΔD95) was 0.75Gy. Basically dose errors and percentage volume error increased as distortion increased. In some special cases, in original plans, the minimum spinal cord max dose error appeared when distortion was 4mm; in MRI‐based plans, the minimum liver ΔV30 appeared when distortion was 3mm. In the example case, mean liver dose was 20.7Gy in 4D MRI‐based plan and 34.2Gy in 4D CT‐based plan.Conclusion:A clinically feasible workflow of 4D MRI‐based treatment planning for liver SBRT has been established. Dose uncertainties of the workflow were generally small, except for large MR geometric distortions (&gt; 3 mm).NIH (1R21CA165384)

SU‐F‐T‐512: A Dosimetric Comparison for Palliative Spine Metastasis Treatments: 3‐D Vs. Conformal Arc

Purpose:Spine metastases have traditionally been treated using a parallel opposed 3‐D technique: an anterior field and a posterior field (AP/PA). This has proven to give the lesions adequate coverage. The downside to this type of treatment is that the full prescription dose covers a large area of the patient and can go through critical organs such as the heart, spine, lungs, bowel, and others depending on the vertebrae being treated. Conformal arc therapy can also be used for this type of treatment. These two techniques will be compared for target coverage and doses to organs at risk (OARs).Methods:20 multi‐vertebra metastases patients were chosen for this study, with a range of vertebrae being treated amongst each case. The original AP/PA treatments were re‐planned with 1–3 conformal arcs placed depending on the location of nearby OARs. The GTV coverage was normalized so that both techniques had equal coverage. The OAR doses and the volume of the 50% prescription dose value were then compared between the two planning techniques.Results:Initial results on average show lower doses for the heart maximum, heart mean, lung V20, spinal cord maximum, and bowel maximum for the conformal arc plans. The AP/PA plans however on average showed lower kidney mean dose, liver mean dose, and parotid mean dose. The 50% prescription dose volume was smaller in all the conformal arc plans except for one.Conclusion:From the preliminary results the conformal arc plans spare critical OARs better than the two field technique, except when treating the vertebrae near the kidneys, liver, and parotids. The conformal arc plans also have a lower volume of the 50% prescription dose value. The data suggests that conformal arcs can be used for certain palliative spine treatments and that this technique should be considered when beginning planning.

SU‐F‐T‐435: Helical Tomotherapy for Craniospinal Irradiation: What We Have Learned from a Multi‐Institutional Study

Purpose:To report cranio‐spinal irradiation (CSI) planning experience, compare dosimetric quality and delivery efficiency with Tomotherapy from different institutions, and to investigate effect of planning parameters on plan quality and treatment time.Methods:Clinical helical tomotherapy IMRT plans for thirty‐nine CSI cases from three academic institutions were retrospectively evaluated. The planning parameters: field width (FW), pitch, modulation factor (MF), and achieved dosimetric endpoints were cross‐compared. A fraction‐dose‐delivery‐timing index (FDTI), defined as treatment time per fraction dose per PTV length, was utilized to evaluate plan delivery efficiency. A lower FDTI indicates higher delivery efficiency. We studied the correlation between planning quality, treatment time and planning parameters by grouping the plans under specific planning parameters. Additionally, we created new plans using 5cm jaw for a subset of plans that used 2.5cm jaw to exam if treatment efficiency can be improved without sacrificing plan quality.Results:There were significant dosimetric differences for organ at risks (OARs) among different institutions (A,B,C). Using the lowest average MF (1.9±0.4) and 5cm field width, C had the highest lung, heart, kidney, liver mean doses and maximum doses for lens. Using the same field width of 5cm, but higher MF (2.6±0.6), B had lower doses to the OARs in the thorax and abdomen area. Most of A's plans were planned with 2.5cm jaw, the plans yielded better PTV coverage, higher OAR doses and slightly shorter FDTI compared to institution B. The replanned 5cm jaw plans achieved comparable PTV coverage and OARs sparing, while saving up to 44.7% treatment time.Conclusion:Plan quality and delivery efficiency could vary significantly in CSI planning on Tomotheapy due to choice of different planning parameters. CSI plans using a 5cm jaw, with proper selection of pitch and MF, can achieve comparable/ better plan quality with shorter delivery time compared to 2.5cm jaw plans.

SU‐D‐204‐02: BED Consistent Extrapolation of Mean Dose Tolerances

Purpose:The safe use of radiotherapy requires the knowledge of tolerable organ doses. For experimental fractionation schemes (e.g. hypofractionation) these are typically extrapolated from traditional fractionation schedules using the Biologically Effective Dose (BED) model. This work demonstrates that using the mean dose in the standard BED equation may overestimate tolerances, potentially leading to unsafe treatments. Instead, extrapolation of mean dose tolerances should take the spatial dose distribution into account.Methods:A formula has been derived to extrapolate mean physical dose constraints such that they are mean BED equivalent. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 14 liver cancer patients previously treated with proton therapy in 5 or 15 fractions, for whom also photon IMRT plans were available.Results:Our work has two main implications. First, in typical clinical plans the dose distribution can have significant effects. When mean dose tolerances are extrapolated from standard fractionation towards hypofractionation they can be overestimated by 10–15%. Second, the shape difference between photon and proton dose distributions can cause 30–40% differences in mean physical dose for plans having the same mean BED. The combined effect when extrapolating proton doses to mean BED equivalent photon doses in traditional 35 fraction regimens resulted in up to 7–8 Gy higher doses than when applying the standard BED formula. This can potentially lead to unsafe treatments (in 1 of the 14 analyzed plans the liver mean dose was above its 32 Gy tolerance).Conclusion:The shape effect should be accounted for to avoid unsafe overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. In addition, tolerances established for a given treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions.

Dosimetric and clinical toxicity comparison of critical organ preservation with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and RapidArc for the treatment of locally advanced cancer of the pancreatic head.

We compared dosimetry and clinical toxicity for 3-dimensional conformal radiotherapy (3D-crt), intensity-modulated radiotherapy (imrt), and RapidArc (Varian Medical Systems, Palo Alto, CA, U.S.A.) in locally advanced pancreatic cancer (lapcc). We hypothesized that the technique with better sparing of organs at risk (oars) and better target dose distributions could lead to decreased clinical toxicity. The study analyzed 280 patients with lapcc who had undergone radiotherapy. The dosimetry comparison was performed using 20 of those patients. Dose-volume histograms for the target volume and the oars were compared. The clinical toxicity comparison used the 280 patients who received radiation with 3D-crt, imrt, or RapidArc. Compared with 3D-crt, RapidArc and imrt both achieved a better conformal index, homogeneity index, V95%, and V110%. Compared with 3D-crt or imrt, RapidArc reduced the V10, V20, and mean dose to duodenum, the V20 of the right kidney, and the liver mean dose. Compared with 3D-crt, RapidArc reduced the V35, and V45 of duodenum, the mean dose to small bowel, and the V15 of right kidney. The incidences of grades 3 and 4 diarrhea (p = 0.037) and anorexia (p = 0.042) were lower with RapidArc than with 3D-crt, and the incidences of grades 3 and 4 diarrhea (p = 0.027) were lower with RapidArc than with imrt. Compared with 3D-crt or imrt, RapidArc showed better sparing of oars, especially duodenum, small bowel, and right kidney. Also, fewer acute grades 3 and 4 gastrointestinal toxicities were seen with RapidArc than with 3D-crt or imrt. A technique with better sparing of oars and better target dose distributions could result in decreased clinical toxicities during radiation treatment for lapcc.

145 Documentation of DVLA guidance provision for patients with brain metastases

Compared with step-and-shoot intensity-modulated radiotherapy (sIMRT) and tomotherapy, volumetric-modulated arc therapy (VMAT) allows additional arc configurations in treatment planning and noncoplanar (NC) delivery. This study was first to compare VMAT planning with sIMRT planning, and the second to evaluate the toxicity of coplanar (C)/NC-VMAT treatment in patients with hepatocellular carcinoma (HCC). Fifteen patients with HCC (7 with left-lobe and 8 with right-lobe tumors) were planned with C-VMAT, C/NC-VMAT, and sIMRT. The median total dose was 49 Gy (range: 40 to 56 Gy), whereas the median fractional dose was 3.5 Gy (range: 3 to 8 Gy). Different doses/fractionations were converted to normalized doses of 2 Gy per fraction using an α/β ratio of 2.5. The mean liver dose, volume fraction receiving more than 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), effective volume (Veff), and equivalent uniform dose (EUD) were compared. C/NC-VMAT in 6 patients was evaluated for delivery accuracy and treatment-related toxicity. Compared with sIMRT, both C-VMAT (p = 0.001) and C/NC-VMAT (p = 0.03) had significantly improved target conformity index. Compared with C-VMAT and sIMRT, C/NC-VMAT for treating left-lobe tumors provided significantly better liver sparing as evidenced by differences in mean liver dose (p = 0.03 and p = 0.007), V10 (p = 0.003 and p = 0.009), V20 (p = 0.006 and p = 0.01), V30 (p = 0.02 and p = 0.002), Veff (p = 0.006 and p = 0.001), and EUD (p = 0.04 and p = 0.003), respectively. For right-lobe tumors, there was no difference in liver sparing between C/NC-VMAT, C-VMAT, and sIMRT. In all patients, dose to more than 95% of target points met the 3%/3 mm criteria. All 6 patients tolerated C/NC-VMAT and none of them had treatment-related ≥ grade 2 toxicity. The C/NC-VMAT can be used clinically for HCC and provides significantly better liver sparing in patients with left-lobe tumors.

Pancreatic cancer planning: Complex conformal vs modulated therapies

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.

Adoption of Hypofractionated Whole-Breast Irradiation for Ductal Carcinoma In Situ Patients After Breast Conservation Surgery

of stage and tumor site between the two groups. The Mann-Whitney U test was used to compare the remaining parameters between the two groups. Analysis was performed using SPSS v.19. Results: There was no significant difference in the distribution of stage (pZ0.19), tumor site (pZ0.63), age (pZ0.99), clinical target volume (CTV) V50 (pZ0.07) and volume of CTV (pZ0.23), heart (pZ0.30), and liver (pZ0.37) between the non-ABC and ABC groups. For all 166 patients, there was a significantly lower ipsilateral lung V5 (pZ0.001), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), whole lung V5 (pZ0.009), whole lung V10 (p<0.001), whole lung V20 (p<0.001), mean whole lung dose (p<0.001), heart V10 (pZ0.005), heart V30 (pZ0.004), heart V40 (pZ0.010), and mean heart dose (pZ0.001) in the ABC group. For 81 patients with a leftsided breast tumor, significantly lower ipsilateral lung V5 (pZ0.004), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (p<0.001), heart V30 (p<0.001), heart V40 (p<0.001), and mean heart dose (p<0.001) were observed in the ABC group. For 85 patients with a right-sided breast tumor, significantly lower ipsilateral lung V10 (pZ0.002), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (pZ0.006), heart V30 (pZ0.008), mean heart dose (p<0.001), liver V30 (p<0.001), and mean liver dose (p<0.001) were observed in the ABC group. Conclusion: For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. Our study showed that mDIBH can significantly reduce the heart and lung dose for all breast cancer patients and also reduce the liver dose for right-sided breast cancer patients. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver. Author Disclosure: C. Lin: None.

Effect of Treatment Time of Day on Radiation Fatigue and Toxicity in Early-Stage Breast Cancer Patients After Breast Conserving Surgery

of stage and tumor site between the two groups. The Mann-Whitney U test was used to compare the remaining parameters between the two groups. Analysis was performed using SPSS v.19. Results: There was no significant difference in the distribution of stage (pZ0.19), tumor site (pZ0.63), age (pZ0.99), clinical target volume (CTV) V50 (pZ0.07) and volume of CTV (pZ0.23), heart (pZ0.30), and liver (pZ0.37) between the non-ABC and ABC groups. For all 166 patients, there was a significantly lower ipsilateral lung V5 (pZ0.001), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), whole lung V5 (pZ0.009), whole lung V10 (p<0.001), whole lung V20 (p<0.001), mean whole lung dose (p<0.001), heart V10 (pZ0.005), heart V30 (pZ0.004), heart V40 (pZ0.010), and mean heart dose (pZ0.001) in the ABC group. For 81 patients with a leftsided breast tumor, significantly lower ipsilateral lung V5 (pZ0.004), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (p<0.001), heart V30 (p<0.001), heart V40 (p<0.001), and mean heart dose (p<0.001) were observed in the ABC group. For 85 patients with a right-sided breast tumor, significantly lower ipsilateral lung V10 (pZ0.002), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (pZ0.006), heart V30 (pZ0.008), mean heart dose (p<0.001), liver V30 (p<0.001), and mean liver dose (p<0.001) were observed in the ABC group. Conclusion: For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. Our study showed that mDIBH can significantly reduce the heart and lung dose for all breast cancer patients and also reduce the liver dose for right-sided breast cancer patients. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver. Author Disclosure: C. Lin: None.

Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Identifying risk factors associated with declining liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) may improve future treatment design. Therefore, clinical and dosimetric parameters were investigated for their association with liver toxicity following SBRT for HCC. Data was analyzed from patients treated on Phase I/II clinical trials of 6 fractions SBRT for HCC. Dose was individually prescribed based on the liver effective volume irradiated and estimated risk of liver toxicity based on a normal tissue complication probability (NTCP) model adjusted for the dose/fraction. Toxicity was defined as an increase in Child-Pugh (CP) score ≥2 within 3 months of SBRT. Patients with baseline lower liver function (CP ≥7, class B) were excluded. Clinical parameters, SBRT details, and cumulative dose-volume histograms (DVH) of the liver (excluding gross tumor) were tested for association with toxicity using logistic regression. A total of 101 patients were evaluable with a baseline CP score of A5 (72%) or A6 (28%), 53% had portal vein HCC thrombus, 80% were male and 91% had underlying liver disease (37% Hepatitis B, 40% Hepatitis C). The median total HCC volume was 121 mL (range 2-1913 mL) and median liver volume (excluding HCC) was 1286 mL (range 766-3967 mL). The median prescribed dose was 36 Gy in 6 fractions (range 27-54 Gy). At 3 months, 26 patients (26%) had toxicity. Portal vein HCC thrombus, CP score of A6, and lower platelet count at baseline were associated with toxicity on univariate analysis. Underlying liver disease was not. Dosimetric parameters of the liver volume receiving at least 5, 10, 15, 20, or 25 Gy, mean liver dose, liver effective volume, NTCP, and dose to 800 mL (D800mL) were significant on univariate analysis and tended to be highly correlated. The spared liver volume, or volumes receiving less than 5, 10, 15, 20 or 25 Gy were not associated with toxicity. Significant associations with toxicity on multivariate analysis were found for baseline CP score (odds ratio (OR) 4.85 [1.47-16.05]), platelet count (OR 0.90 [0.82-0.98] per 10 unit increase, median 108x109/L with toxicity, vs. 150x109/L without), mean liver dose (OR 1.33 [1.04-1.69], median 17.0 Gy with toxicity vs. 15.2 Gy without) and D800mL (OR 1.11 [1.02-1.21], median 14.3 Gy with toxicity vs. 6.0 Gy without). For CP class A patients, baseline CP score, platelet count, mean liver dose, and D800mL are associated with an increase in CP score by 2 or more 3 months following SBRT for HCC.

Dynamic tumor-tracking radiotherapy with real-time monitoring for liver tumors using a gimbal mounted linac

PurposeDynamic tumor-tracking stereotactic body radiotherapy (DTT-SBRT) for liver tumors with real-time monitoring was carried out using a gimbal-mounted linear accelerator and the efficacy of the system was determined. In addition, four-dimensional (4D) dose distribution, tumor-tracking accuracy, and tumor-marker positional variations were evaluated. Materials and methodsA fiducial marker was implanted near the tumor prior to treatment planning. The prescription dose at the isocenter was 48–60Gy, delivered in four or eight fractions. The 4D dose distributions were calculated with a Monte Carlo method and compared to the static SBRT plan. The intrafractional errors between the predicted target positions and the actual target positions were calculated. ResultsEleven lesions from ten patients were treated successfully. DTT-SBRT allowed an average 16% reduction in the mean liver dose compared to static SBRT, without altering the target dose. The average 95th percentiles of the intrafractional prediction errors were 1.1, 2.3, and 1.7mm in the left–right, cranio-caudal, and anterior–posterior directions, respectively. After a median follow-up of 11months, the local control rate was 90%. ConclusionsOur early experience demonstrated the dose reductions in normal tissues and high accuracy in tumor tracking, with good local control using DTT-SBRT with real-time monitoring in the treatment of liver tumors.

Clinical utility of gadoxetate disodium-enhanced hepatic MRI for stereotactic body radiotherapy of hepatocellular carcinoma.

To investigate the utility of gadoxetate disodium-enhanced hepatic MRI (EOB-MRI) for stereotactic body radiotherapy (SBRT) to treat hepatocellular carcinoma (HCC). We divided 30 HCC patients who underwent SBRT into group A (no change in their Child-Pugh score 6months post-SBRT) and group B (increased score 6months post-SBRT). EOB-MRI was performed before and 6months after SBRT. We calculated the liver-spleen contrast (LSC) ratio for each radiation dose area on hepatobiliary phase scans (LSCbefore using images obtained before SBRT and LSCafter using images acquired after SBRT) and the weighted LSC (W-LSC) as: [(mean LSCbefore (0-30Gy) × liver volume (0-30Gy)+mean LSCbefore (30Gy-) × liver volume (30Gy-))/total liver volume]. Then we compared the W-LSC, percentage of the liver volume exposed to >20Gy (V20), and mean liver dose in the two groups. The LSCafter at 48, 40, and 30Gy to the liver was statistically lower than the unirradiated area of the liver (p<0.01). Univariate analysis showed that only W-LSC was significantly associated with group B (p=0.02). W-LSC was a useful parameter for predicting changes in hepatic function after SBRT.