Search

Purpose: To describe the long-term outcomes of a 5-fraction normal tissue tolerance adapted strategy for the management of oligometastases (OM)., Methods and Materials: Patients with histologically confirmed solid tumors, ≤5 extracranial metastases, suitable for a definitive approach for all metastatic lesions, at least one lesion suitable for Stereotactic Body Radiotherapy (SBRT), Eastern Coooperative Oncology Group Performance Status ≤2 were eligible. Treatment intervention was a 5-fraction (25-55 Gy) normal tissue adapted dosing strategy. The primary outcome was cumulative local progression rate at 12 months., Results: Between March 2013 and January 2018, 137 patients started SBRT. Median follow-up was 35.7 months. In addition, 107 (78%) patients had a solitary OM. The mean planning target volume D 95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D 95 was highest for lung lesions (48.7 [standard deviation, 4.7]; biological effective dose using an alpha/beta ratio of 10, 96.1) Gy but was <40 Gy for all other anatomic sites. Two grade 3 toxicities (gastrointestinal bleed) were observed with stomach D 0.05 30.3 Gy and 30.4 Gy. The cumulative local progression rate at 12 of 36 months was 16.1% (95% CI, 10-22) and 38.3% (95% CI 30-46.7); overall survival was 90% and 37%, and progression free survival was 58% and 19%, respectively. Mean symptom burden (Edmonton Symptom Assessment Total Score) worsened in patients with progressive disease (+8.8) at 12 months and was paralleled by changes in mean European Organization for Research and Treatment Quality of Life Core Questionnaire Summary Score and Global Health Quality of Life Score. Systemic therapy was initiated in 55% of patients at an average of 12.7 (standard deviation 12.4) months., Conclusions: If long-term progression free survival is the primary goal of therapy, SBRT for OM achieved this in <20% of patients attributable to a high risk of distant failure. Favorable local progression free survival is accompanied by preservation of quality of life, avoidance of symptom progression and reduced need of antineoplastic therapies at 12 months. Information on symptom burden, quality of life, as well as pattern of antineoplastic therapy use after progressive disease is useful to support conversations between patients, families, and health care providers. Strategies to improve patient selection and reduce distant progression rate remain a priority for further study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour control in silico in several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), using 18 F-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10 -5 ) well above levels required to completely ablate a ∼10 cm 3 tumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity., (© 2021 Institute of Physics and Engineering in Medicine.)

Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT)., Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed., Results: 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT., Conclusions: SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura. A. Dawson reports patent/License Fees/Copyright: Raysearch., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America., Methods: Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates., Results: In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%., Conclusions: SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT., Competing Interests: Conflict of interest statement L.A.D has a licencing agreement for Raysearch image registration software (unrelated). A.B. has a consulting/advisory role with Astra Zeneca. K.C. received research funding from BTG and Varian Medical Systems. M.F. has a consulting/advisory role in GenomeDx, Myriad Pharmaceuticals, NanoString Technologies and Varian Medical Systems. She receives honoraria from Medivation/Astellas (also in Speaker's bureau); Myriad Pharmaceuticals; Reflexion Medical and research funding from Celgene (I); Varian Medical Systems (Inst). She also received travel expenses from GenomeDx and has a pending patent for RadioType Dx, a biomarker test. A.S.M, E.A., D.O., R.D., J.K., J.R., R.W., C.M., J.B., C.C. and T.S.L. had no conflicts of interest to declare., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the baseline albumin-bilirubin (ALBI) score as a predictor of toxicity and survival in a prospective cohort of Western patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) in 2 prospective trials., Methods and Materials: The study included 102 patients with Child-Pugh class A liver disease who received 6-fraction SBRT for HCC. Univariate and multivariable logistic regression investigated factors associated with toxicity, defined as an increase in Child-Pugh score ≥ 2 within 3 months of SBRT. Univariate and multivariable Cox regression analyses investigated factors predictive of overall survival (OS). The ALBI score was analyzed as a continuous and binary variable in separate analyses., Results: On multivariable analysis of toxicity, including the ALBI score as a continuous variable, the ALBI score (odds ratio [OR] per 0.1-unit increase, 1.51; 95% confidence interval [CI] 1.23-1.85; P = .00074), mean liver dose (OR, 1.31; 95% CI 1.02-1.68; P = .036), and dose received by 800 cm 3 of normal liver (OR, 1.10; 95% CI 1.01-1.20; P = .028) were significant. When the ALBI score was included as a dichotomous variable, the ALBI grade remained a significant predictor of toxicity (OR, 7.44; 95% CI 2.34-23.70; P = .00069). On multivariable analysis of OS, including the ALBI score as a continuous variable, the ALBI score (hazard ratio [HR] per 0.1-unit increase, 1.09; 95% CI 1.03-1.17; P = .004), tumor thrombus (HR, 1.94; 95% CI 1.23-3.07; P = .004), and treatment in trial 1 versus trial 2 (HR, 1.92; 95% CI 1.23-3.03; P = .004) were significant. Similarly, when the ALBI score was included as a binary variable, the ALBI grade, tumor thrombus, and trial were significant predictors of OS. When the ALBI score was considered, the Child-Pugh score (A6 vs A5) was not significant in multivariable models analyzing toxicity or survival. Concordance statistics indicated models containing the ALBI score were superior to those containing the Child-Pugh score., Conclusions: The baseline ALBI score was more discriminating than the Child-Pugh score in predicting OS and toxicity in patients with Child-Pugh class A liver disease. The ALBI score should be used as a factor for stratification in future HCC SBRT trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To report mature outcomes of prospective phase 1 and 2 studies of stereotactic body radiation therapy (SBRT) for the treatment of colorectal liver metastases (CLMs)., Methods and Materials: Patients with histologically confirmed CLMs unsuitable for resection or standard therapies were eligible for sequential phase 1 and 2 studies conducted from 2003 to 2012., Results: Of 60 patients treated, 82% had received previous chemotherapy, 23% had undergone previous focal liver treatment, and 38% had extrahepatic disease at the time of SBRT. The median number of gross tumor volume (GTV) targets per patient was 1 (range, 1-6), with a median total target volume of 117.7 cm 3 (range, 6.7-3115.4 cm 3 ). The median minimum dose to the GTV was 37.6 Gy (range, 22.7-62.1 Gy) in 6 fractions over a period of 2 weeks. Other than 1 case of grade 3 nausea, there were no acute toxicities greater than grade 2. With a median follow-up period of 28.1 months for survivors, no gastrointestinal bleed or biliary or liver toxicity was seen. The local control rate per lesion at 1 and 4 years was 49.8% and 26.2%, respectively. Increasing minimum dose to the GTV was associated with improved local control (P=.003). Median overall survival was 16.0 months (95% confidence interval, 11.9-20.5 months). On multivariate analysis, improved survival was associated with smaller total GTV (P=.017), performance status of 0 or 1 (P=.007), no extrahepatic disease at the time of treatment (P=.005), and local control of targeted liver disease (P=.001). Two long-term survivors remain disease free at 49 and 125 months., Conclusions: Six-fraction SBRT for CLM is safe and may be associated with long-term cure. Local control was significantly associated with delivered dose and was lower than seen in other studies using a higher SBRT dose. Survival was associated with smaller tumor volume, absence of extrahepatic disease, performance status of 0 or 1, and local control of treated liver lesions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The 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 Materials: Between 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., Results: Seventy 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)., Conclusions: Liver 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., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is limited information on the use of stereotactic body radiotherapy (SBRT) as a bridge to liver transplantation for hepatocellular carcinoma and no study comparing its efficacy to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). We aimed to ascertain the safety and efficacy of SBRT on an intention-to-treat basis compared with TACE and RFA as a bridge to liver transplantation in a large cohort of patients with hepatocellular carcinoma., Methods: Outcomes between groups were compared from the time of listing and from the time of transplant. Between July 2004 and December 2014, 379 patients were treated with either SBRT (n=36, SBRT group), TACE (n=99, TACE group) or RFA (n=244, RFA group)., Results: The drop-out rate was similar between groups (16.7% SBRT group vs. 20.2% TACE group and 16.8% RFA group, p=0.7); 30 patients were transplanted in the SBRT group, 79 in the TACE group and 203 in the RFA group. Postoperative complications were similar between groups. Patients in the RFA group had more tumor necrosis in the explant. The 1-, 3- and 5-year actuarial patient survival from the time of listing was 83%, 61% and 61% in the SBRT group vs. 86%, 61% and 56% in the TACE group, and 86%, 72% and 61% in the RFA group, p=0.4. The 1-, 3- and 5-year survival from the time of transplant was 83%, 75% and 75% in the SBRT group vs. 96%, 75% and 69% in the TACE group, and 95%, 81% and 73% in the RFA group, p=0.7., Conclusions: In conclusion, SBRT can be safely utilized as a bridge to LT in patients with HCC, as an alternative to conventional bridging therapies., Lay Summary: Patients with liver cancer included in the waiting list for liver transplantation are at risk of tumor progression and death. Stereotactic body radiotherapy may be a good alternative to conventional therapies to reduce this risk., (Copyright © 2017 European Association for the Study of the Liver. All rights reserved.)

Purpose: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC)., Methods and Materials: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned., Results: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum., Conclusions: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial., (Copyright © 2016. Published by Elsevier Inc.)

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases., Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board-approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm(3) (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm(3) gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping., Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose-response predictor than the minPTV dose., Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose-response outcomes should increase the concordance between the planned and delivered doses., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver., Methods and Materials: Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were also treated., Results: The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P = .17) or overall survival (P = .088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT-Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P = .001) and 0.88 (95% CI 0.82-0.95; P = .001), respectively. Tumor size was inversely correlated with survival., Conclusions: Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and warrants comparison against other liver-directed therapies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort., Methods: Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging ≥ 3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for > 90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose., Results: Forty-seven (72%) patients had ≥ 1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had ≥ 2 regimens. The median follow-up was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose (P = .0015), dose/fraction (P = .003), and BED (P = .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P = .046), and sustained local control was closely correlated (P = .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control > 90% is 46 to 52 Gy in 3 fractions., Conclusions: Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of ≥ 48 Gy should be considered, if normal tissue constraints allow., (Cancer 2011 © 2011 American Cancer Society.)

Purpose: To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases., Patients and Methods: Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks., Results: Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months)., Conclusion: Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.

Purpose: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma.Methods and Materials: 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.Results: 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 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). 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, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk.Conclusions: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk. [ABSTRACT FROM AUTHOR]