Pulmonary interstitial lymphography: A prospective trial with potential impact on stereotactic ablative radiotherapy planning for early-stage lung cancer.

This prospective feasibility trial investigated pulmonary interstitial lymphography to identify thoracic primary nodal drainage (PND). A post-hoc analysis of nodal recurrences was compared with PND for patients with early-stage lung cancer; larger studies are needed to establish correlation. Exploratory PND-inclusive stereotactic ablative radiotherapy plans were assessed for dosimetric feasibility.

Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas.

Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9-26.1 months), while median LPFS was 9 months (95% CI: 6.2-11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0-1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

Evidence-Based Integration of Yttrium-90 Radioembolization in the Contemporary Management of Hepatic Metastases from Colorectal Cancer.

Hepatic metastases are common in patients with metastatic colorectal cancer and are frequently the most life-threatening source of morbidity and mortality. The contemporary management of patients with liver-dominant or liver-only metastatic colorectal cancer is characterized by resection of metastases when feasible and successive lines of systemic treatment regimens consisting of chemotherapy drugs and/or targeted biological agents. Yttrium-90 radioembolization has emerged as a promising liver-directed therapy for patients with unresectable colorectal cancer liver metastases (CLM). The integration of radioembolization into the current treatment algorithm for unresectable CLM is dependent on the line of therapy it is being considered and whether it is to be used alone or in combination with systemic treatment options. This article provides background information on the current management of CLM and uses this framework to discuss the existing data that define when and how radioembolization can benefit patients with CLM.

Quantification of Activity Lost to Delivery-System Residual and Decay in Yttrium-90 Radioembolization.

PURPOSE: To measure the decay activity loss and delivery system residual activity loss of yttrium-90 (Y90) radioembolization treatments across resin and glass microsphere activities. MATERIALS AND METHODS: For Y90 administrations between December 2009 and June 2017 at the study institution, the prescribed activity, prepared activity, and delivered activity were recorded. Six hundred sixty-two administrations were reviewed-345 glass (0.21-8.52 GBq) and 317 resin (0.18-3.28 GBq). Twenty-five patients (all resin) were excluded for arterial stasis or catheter clogging. The percentage and actual losses of activity lost to decay and to delivery system residual were calculated for glass and resin microspheres. RESULTS: The median time between activity premeasurement and administration was 2.20 hours, resulting in a median activity lost to decay of 0.030 GBq or 2.35%, with no significant difference observed between glass and resin despite differences in preparation (P = .0697). Resin showed significantly higher activity lost to delivery system residual than glass (0.039 GBq vs 0.010 GBq, 3.01% vs 0.61%, P < .001). The percent activity lost to residual varied with activity prepared, with a maximum of 20.1% and 16.2% for the smallest activities of resin and glass, respectively. CONCLUSIONS: Residual activity loss differs between glass and resin microspheres. For resin microspheres in particular, percent residual activity loss increases with lower prepared activities. Protocols for activity calculation and preparation, patient dosimetry, and regulatory compliance must take these losses into consideration prospectively.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

PURPOSE: The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. METHODS: The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. RESULTS: Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. CONCLUSION: Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Yttrium-90 Radioembolization for Unresectable Combined Hepatocellular-Cholangiocarcinoma.

PURPOSE: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare mixed cell type primary liver cancer with limited data to guide management. Transarterial radioembolization with yttrium-90 microspheres (RE) is an emerging treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. This study explored the safety and efficacy of RE for unresectable cHCC-CC. METHODS: Patients with histopathologically confirmed cHCC-CC treated with RE were retrospectively evaluated. Clinical and biochemical toxicities were assessed using the Common Toxicity Criteria for Adverse Events v4.03. Radiological response was analyzed using the Response Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST criteria. Survival times were calculated and prognostic variables identified. RESULTS: Ten patients (median age 59 years; six men, four women) with unresectable cHCC-CC underwent 14 RE treatments with resin (n = 6 patients) or glass (n = 4 patients) microspheres. Clinical toxicities were limited to grade 1-2 fatigue, anorexia, nausea, or abdominal pain. No significant biochemical toxicities were observed. Median overall survivals from the first RE treatment and from initial diagnosis were 10.2 and 17.7 months, respectively. Six of seven patients with elevated tumor biomarker levels before RE showed decreased levels after treatment (median decrease of 72%, range 13-80%). Best hepatic radiological response was 60% partial response and 40% stable disease by modified RECIST, and 100% stable disease by RECIST v1.1. Poor performance status and the presence of macrovascular invasion were identified as predictors of reduced survival after RE. CONCLUSION: RE appears to be a safe and promising treatment option for patients with unresectable cHCC-CC. LEVEL OF EVIDENCE: Level 4.

The Role of Dual-Phase Cone-Beam CT in Predicting Short-Term Response after Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To identify computational and qualitative features derived from dual-phase cone-beam CT that predict short-term response in patients undergoing transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 43 patients with 59 HCCs. Six features were extracted, including intensity of tumor enhancement on both phases and characteristics of the corona on the washout phase. Short-term response was evaluated by modified Response Evaluation Criteria in Solid Tumors on follow-up imaging, and extracted features were correlated to response using univariate and multivariate analyses. RESULTS: Univariate and multivariate analyses did not reveal a correlation between absolute and relative tumor enhancement characteristics on either phase with response (arterial P = .21; washout P = .40; ∆ P = .90). On multivariate analysis of qualitative characteristics, the presence of a diffuse corona was an independent predictor of incomplete response (P = .038) and decreased the odds ratio of objective response by half regardless of tumor size. CONCLUSIONS: Computational features extracted from contrast-enhanced dual-phase cone-beam CT are not prognostic of response to transarterial chemoembolization in patients with HCC. HCCs that demonstrate a diffuse, patchy corona have reduced odds of achieving complete response after transarterial chemoembolization and should be considered for additional treatment with an alternative modality.

Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery.

PURPOSE: To evaluate safety of resin microsphere radioembolization (RE) without prophylactic embolization of the gastroduodenal artery (GDA). MATERIALS AND METHODS: Between July 2013 and April 2015, all patients undergoing RE with resin microspheres for liver-dominant metastatic disease were treated without routine embolization of the GDA. Selective embolization of distal hepaticoenteric vessels was performed if identified by digital subtraction angiography, cone-beam computed tomography, or technetium-99m macroaggregated albumin scintigraphy. Resin microspheres were administered using 5% dextrose flush distal to the origin of the GDA in lobar or segmental fashion, with judicious use of an antireflux microcatheter in recognized high-risk situations. Gastrointestinal toxicity was evaluated by the performing physician for at least 3 months. RESULTS: RE with resin microspheres was performed in 62 patients undergoing 69 treatments. During planning angiography, embolization of 0 or 1 vessel (median, 1; range, 0-4) was performed in 86% of patients, most commonly the right gastric and supraduodenal arteries. Prophylactic embolization of the GDA was performed in only 2 patients (3%). In 6 treatments (9%), adjunctive embolization was required immediately before RE, and an antireflux microcatheter was used in 14% of treatments. Clinical follow-up was available in 60 of 62 patients (median, 134 d; range, 15-582 d). No signs or symptoms of gastric or duodenal ulceration were observed. CONCLUSIONS: RE using resin microspheres without embolization of the GDA can be performed safely.

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.

PURPOSE: To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. MATERIALS AND METHODS: From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. RESULTS: Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. CONCLUSION: Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.

Management of High Hepatopulmonary Shunting in Patients Undergoing Hepatic Radioembolization.

PURPOSE: To review the safety of hepatic radioembolization (RE) in patients with high (≥ 10%) hepatopulmonary shunt fraction (HPSF) using various prophylactic techniques. MATERIALS AND METHODS: A review was conducted of 409 patients who underwent technetium 99m-labeled macroaggregated albumin scintigraphy before planned RE. Estimated pulmonary absorbed radiation doses based on scintigraphy and hepatic administered activity were calculated. Outcomes from dose reductions and adjunctive catheter-based prophylactic techniques used to reduce lung exposure were assessed. RESULTS: There were 80 patients with HPSF ≥ 10% who received RE treatment (41 resin microspheres for metastases, 39 glass microspheres for hepatocellular carcinoma). Resin microspheres were used in 17 patients according to consensus guideline-recommended dose reduction; 38 patients received no dose reduction because the expected lung dose was < 30 Gy. Prophylactic techniques were used in 25 patients (with expected lung dose ≤ 74 Gy), including hepatic vein balloon occlusion, variceal embolization, or bland arterial embolization before, during, or after RE delivery. Repeated scintigraphy after prophylactic techniques to reduce HPSF in seven patients demonstrated a median change of -40% (range, +32 to -69%). Delayed pneumonitis developed in two patients, possibly related to radiation recall after chemoembolization. Response was lower in patients treated with resin spheres with dose reduction, with an objective response rate of 13% and disease control rate of 47% compared with 56% and 94%, respectively, without dose reduction (P = .023, P = .006). CONCLUSIONS: Dose reduction recommendations for HPSF may compromise efficacy. Excessive shunting can be reduced by prophylactic catheter-based techniques, which may improve the safety of performing RE in patients with high HPSF.

Watershed Hepatocellular Carcinomas: The Risk of Incomplete Response following Transhepatic Arterial Chemoembolization.

PURPOSE: Hepatocellular carcinomas (HCCs) bridging two or more Couinaud-Bismuth segments of the liver ("watershed tumors") can recruit multiple segmental arteries. The primary hypothesis of this study was that fewer watershed tumors show complete response (CR) after chemoembolization, with shorter time to local recurrence. Secondary analysis on the impact on transplantation eligibility in the presence of progressive disease was also performed. MATERIALS AND METHODS: A total of 155 transplantation-eligible patients whose HCC met Milan criteria (watershed, n = 83; nonwatershed, n = 72) and was treated with chemoembolization were included. Cone-beam computed tomography (CT) was used for guidance and for confirmation of circumferential uptake. Local response to chemoembolization per modified Response Evaluation Criteria In Solid Tumors and local disease-free survival (DFS) for the index tumor were calculated. Differences were assessed by univariate and multivariate analyses. RESULTS: CR after a single of chemoembolization was observed in 55.4% of watershed tumors and in 72.2% of nonwatershed tumors (P = .045). Estimated DFS intervals were 151 days (95% confidence interval [CI], 93-245 d) and 336 days (95% CI, 231-747 d; P = .040) in the watershed and nonwatershed groups, respectively. Worse DFS was observed with a Model for End-Stage Liver Disease score > 20 (P = .0001), higher Child-Pugh-Turcotte score (P = .049), and watershed location (P = .040). Waiting list drop-off rates were statistically similar between groups. CONCLUSIONS: Hepatocellular carcinomas located in the watershed region of the liver have a poorer response to chemoembolization than those located elsewhere. These tumors are associated with worse DFS and require additional treatments to maintain transplantation eligibility per Milan criteria. Cone-beam CT can identify crossover supply and confirm complete geographic drug uptake, possibly reducing (but not eliminating) the risk of incomplete response.

Fusion dual-tracer SPECT-based hepatic dosimetry predicts outcome after radioembolization for a wide range of tumour cell types.

PURPOSE: Fusion dual-tracer SPECT imaging enables physiological rather than morphological voxel-based partitioning and dosimetry for (90)Y hepatic radioembolization (RE). We evaluated its prognostic value in a large heterogeneous cohort of patients with extensive hepatic malignancy. METHODS: A total of 122 patients with primary or secondary liver malignancy (18 different cell types) underwent SPECT imaging after intraarterial injection of (99m)Tc macroaggregated albumin (TcMAA) as a simulation of subsequent (90)Y microsphere distribution, followed by administration of an excess of intravenous (99m)Tc-labelled sulphur colloid (TcSC) as a biomarker for functional liver, and a second SPECT scan. TcMAA distribution was used to estimate (90)Y radiation absorbed dose in tumour (D T) and in functional liver. Laboratory and clinical follow-up were recorded for 12 weeks after RE, and radiographic responses according to (m)RECIST were evaluated at 3 and 6 months. Dose-response relationships were determined for efficacy and toxicity. RESULTS: Patients were treated with a median of 1.73 GBq activity of resin microspheres (98 patients) or glass microspheres (24 patients), in a whole-liver approach (97 patients) or a lobar approach (25 patients). The objective response rate was 41% at 3 months and 48% at 6 months. Response was correlated with D T (P < 0.01). Median overall survival was 10.1 months (95% confidence interval 7.4 - 12.8 months). Responders lived for 36.0 months compared to 8.7 months for nonresponders (P < 0.01). Stratified for tumour cell type, D T was independently associated with survival (P < 0.01). Absorbed dose in functional liver was correlated with toxicity grade change (P < 0.05) and RE-induced liver disease (P < 0.05). CONCLUSION: Fusion dual-tracer SPECT imaging offers a physiology-based functional imaging tool to predict efficacy and toxicity of RE. This technique can be refined to define dosing thresholds for specific tumour types and treatments, but appears generally predictive even in a heterogeneous cohort.

Emergent salvage direct intrahepatic portocaval shunt procedure for acute variceal hemorrhage.

PURPOSE: To review the safety and effectiveness of direct intrahepatic portocaval shunt (DIPS) creation with variceal embolization for acute variceal hemorrhage after a failed transjugular intrahepatic portosystemic shunt (TIPS) creation attempt or in patients with prohibitive anatomy. MATERIALS AND METHODS: Transjugular intrahepatic portosystemic shunt and DIPS procedures performed for variceal hemorrhage between January 2008 and July 2014 were reviewed. The default procedure was TIPS creation, with DIPS creation reserved for patients with unfavorable anatomy or who had technically unsuccessful TIPS creation. Thirteen patients underwent DIPS creation (mean age, 60 y ± 12; Child-Pugh class A/B/C, 8%/62%/30%; Model for End-stage Liver Disease score, 15 ± 5; range, 8-26) and 117 underwent TIPS creation. Four patients underwent a TIPS attempt and were converted to DIPS creation upon technical failure; 9 were treated primarily with DIPS creation because of preprocedural imaging revealing unfavorable anatomy (intrahepatic portal thrombosis, n = 2; venous distortion from prior hepatic resections, n = 2; severely angulated hepatic veins, n = 5). RESULTS: Direct intrahepatic portocaval shunt creation with variceal embolization (six gastric or esophageal; seven stomal, duodenal, or rectal) was successful in all patients; 11 also had concomitant variceal sclerotherapy. Mean DIPS procedure time was less than 2 hours. There was 1 major procedural complication. During a mean follow-up of 13.0 months ± 15.5, 1 patient developed DIPS thrombosis and recurrent hemorrhage; 1 patient underwent successful transplantation. Two deaths were observed within 30 days, neither associated with recurrent hemorrhage. CONCLUSIONS: Direct intrahepatic portocaval shunt creation appears to be a safe, expedient, and effective treatment for patients with acute variceal hemorrhage who are poor anatomic candidates for TIPS creation or who have undergone unsuccessful TIPS creation attempts.

Optimal imaging surveillance schedules after liver-directed therapy for hepatocellular carcinoma.

PURPOSE: To optimize surveillance schedules for the detection of recurrent hepatocellular carcinoma (HCC) after liver-directed therapy. MATERIALS AND METHODS: New methods have emerged that allow quantitative analysis and optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. These methods were applied to 1,766 consecutive chemoembolization, radioembolization, and radiofrequency ablation procedures performed on 910 patients between 2006 and 2011. Computed tomography or magnetic resonance imaging performed just before repeat therapy was set as the time of "recurrence," which included residual and locally recurrent tumor as well as new liver tumors. Time-to-recurrence distribution was estimated by Kaplan-Meier method. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay. RESULTS: Recurrence is 6.5 times more likely in the first year after treatment than in the second. Therefore, screening should be much more frequent in the first year. For eight time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared with published schedules and is cost-effective. CONCLUSIONS: The calculated optimal surveillance schedules include shorter-interval follow-up when there is a higher probability of recurrence and longer-interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay or diagnostic delay can be optimized within a specified acceptable cost.

Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer.

PURPOSE: To calculate absorbed radiation doses in patients treated with resin microspheres prescribed by the body surface area (BSA) method and to analyze dose-response and toxicity relationships. MATERIALS AND METHODS: A retrospective review was performed of 45 patients with colorectal carcinoma metastases who received single-session whole-liver resin microsphere radioembolization. Prescribed treatment activity was calculated using the BSA method. Liver volumes and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with toxicity and radiographic and biochemical response. RESULTS: The standard BSA-based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL) (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method. Patients with larger livers were relatively underdosed, and patients with smaller livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05) but also responded better to the treatment than patients who received D(WL)< 50 Gy (disease control, 88% vs 24%; P < .01). CONCLUSIONS: Using the standard BSA formula, the administered activity did not correlate with D(WL). Based on this short-term follow-up after salvage therapy in patients with late stage metastatic colorectal carcinoma, dose-response and dose-toxicity relationships support using a protocol based on liver volume rather than BSA to prescribe the administered activity.