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Published online before print March 18, 2008, 10.1148/radiol.2472062029
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(Radiology 2008;247:507-515.)
© RSNA, 2008

Nuclear Medicine

Unresectable Chemorefractory Liver Metastases: Radioembolization with 90Y Microspheres—Safety, Efficacy, and Survival1

Kent T. Sato, MD, Robert J. Lewandowski, MD, Mary F. Mulcahy, MD, Bassel Atassi, MD, Robert K. Ryu, MD, Vanessa L. Gates, MS, Albert A. Nemcek, Jr, MD, Omar Barakat, MD, Al Benson, III, MD, Robert Mandal, MD, Mark Talamonti, MD, Ching-Yee O. Wong, MD, PhD, Frank H. Miller, MD, Steven B. Newman, MD, John M. Shaw, MD, Kenneth G. Thurston, MA, Reed A. Omary, MD, and Riad Salem, MD, MBA

1 From the Department of Radiology, Section of Interventional Radiology (K.T.S., R.J.L., M.F.M., B.A., R.K.R., V.L.G., A.A.N., O.B., F.H.M., R.A.O., R.S.), Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center (M.F.M., A.B., S.B.N., J.M.S., R.S.), Department of Nuclear Medicine (V.L.G.), and Department of Surgery, Robert H. Lurie Comprehensive Cancer Center (M.T.), Northwestern University, 676 N Saint Clair St, Suite 800, Chicago, IL 60611; North Shore Oncology and Hematology Associates, Libertyville, Ill (R.M.); Department of Nuclear Medicine, Beaumont Hospital, Royal Oak, Mich (C.Y.O.W.); and West Grove, Pa (K.G.T.). Received November 28, 2006; revision requested January 24, 2007; revision received June 27; accepted August 1; final version accepted October 15. Address correspondence to R.S. (e-mail: r-salem{at}northwestern.edu)


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 (90Y) glass microspheres.

Materials and Methods: Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of 90Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients.

Results: There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors.

Conclusion:90Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Clinical trial registration no. NCT00532740 [ClinicalTrials.gov] .

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Radioembolization has been shown to be effective in the treatment of unresectable hepatocellular carcinoma, as well as unresectable colon carcinoma metastases (1–4). Radioembolization is a local-regional liver-directed therapy that involves transcatheter delivery of particles embedded with the radioisotope yttrium 90 (90Y). Particles are infused through a catheter into the hepatic artery where they travel distally and lodge at the tumor arteriolar level. 90Y is a pure beta emitter that delivers a high dose of radiation to the tumor, which results in necrosis. One of the clinically available products for radioembolization is TheraSphere (MDS Nordion, Ottawa, Ontario, Canada). TheraSphere has received a humanitarian device exemption from the Food and Drug Administration for use in hepatocellular carcinoma. Investigators are directed to published Food and Drug Administration guidelines for the use of humanitarian device exemptions in disease conditions other than the approved indication. The use of this therapy for hepatocellular carcinoma, colorectal carcinoma, and mixed neoplasia has been previously reported (1–11). Although short-term results of radioembolization for metastatic liver disease are promising (response rates, 30%–60%), the purpose of our study was to prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with 90Y glass microspheres.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
One author (R.S.) is a consultant for MDS Nordion and has disclosed a potential conflict of interest. None of the other authors have disclosed a conflict. The data were controlled by all authors. No industry support for this study was provided.

Eligibility Criteria
Between 2002 and 2006, 137 patients with chemorefractory liver-dominant metastases from various primary malignancies were treated at two institutions (Northwestern University and Beaumont Hospital) and were prospectively enrolled in this open-label phase II study. All patients underwent preprocedural imaging with computed tomography (CT). Magnetic resonance (MR) imaging was performed in the setting of contrast material allergies or renal dysfunction. Liver function and tumor markers were evaluated when appropriate. Positron emission tomography (PET) was used to assess response in patients with conditions commonly assessed by using PET, such as colorectal and breast cancers. Survival and follow-up data from both institutions were obtained and included in this analysis. The institutional review boards from both institutions approved our Health Insurance Portability and Accountability Act–compliant study, and all patients provided informed consent.

Inclusion criteria were as follows: (a) chemorefractory or progressive liver-dominant metastases; (b) being a nonsurgical candidate; (c) Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; (d) noncompromised pulmonary function; (e) the ability to undergo angiography and selective visceral catheterization; (f) adequate hematology (granulocyte count ≥ 1.5 x 109/L, platelets ≥ 50 x 109/L) and renal function (creatinine level ≤ 2.0 mg/dL [176.8 µmol/L]); (g) adequate liver function (bilirubin level ≤ 2.0 mg/dL [34.2 µmol/L]); and (h) limited extrahepatic disease not deemed clinically important by the referring physician. Exclusion criteria were as follows: (a) other planned systemic or local-regional therapy for their cancer; (b) liver failure (bilirubin level > 2.0 mg/dL [34.2 µmol/L]); (c) evidence of any uncorrectable flow to the gastrointestinal tract observed at angiography or technetium 99m macroaggregated albumin imaging; and (d) greater than 30 Gy (16.5 mCi) estimated to be delivered to the lungs in a single administration or 50 Gy in multiple administrations.

Patient Referral and Work-up
Progression of liver metastases in patients was documented by using two consecutive imaging studies (CT or MR imaging), and patients were referred to interventional radiology for treatment by the attending medical or surgical oncologists (M.F.M., A.B., R.M., M.T., S.B.N., J.M.S.). After obtaining relevant laboratory test results (liver function tests, complete blood count, metabolic panel) and clinical history, patients underwent pretreatment angiography with selective visceral catheterization. Preprocedural angiography was performed to evaluate anatomy and identify vessels that required intervention such as embolization. The estimated shunt fraction of 90Y to the lungs was also calculated at that time (1,12–17). Baseline images were evaluated for the percentage of tumor burden in the liver, presence of extrahepatic metastases, portal venous occlusion, and the overall number of lesions.

Treatment and Follow-up Evaluation
Depending on the extent of disease within the liver at presentation, patients received either bilobar (right and left lobe) or unilobar treatment. For bilobar treatment, the first lobe treatment was followed by the second lobe treatment approximately 30 days later. No whole liver infusions were performed. Lobar treatment was targeted to deliver 120 Gy by using previously published dosimetry techniques (18). Infusion of 90Y microspheres (TheraSphere) was performed by four interventional radiologists (R.S., R.K.R., K.T.S., and R.J.L. with 8, 8, 5, and 2 years of experience, respectively). Baseline imaging with spiral CT or dynamic gadolinium-enhanced MR imaging was performed prior to treatment for all patients. For those patients receiving bilobar treatment, imaging was repeated just prior to the second lobar treatment (30–45 days) and again at 3 months after first imaging. Patients undergoing unilobar treatment were scheduled for imaging every 30 days and then once every 3 months. Patients were followed up with imaging every 3 months until the patient died. Laboratory and clinical toxicity results (including lymphocytes) were assessed at each clinic visit and were classified by using the National Cancer Institute common toxicity criteria (version 3.0) (grade 0 = normal, grade 1 = more than upper limit normal [ULN] to 1.5 times ULN, grade 2 = more than 1.5 to three times ULN, grade 3 = more than three to 10 times ULN, grade 4 = more than 10 times ULN). Procedural complications were classified by using the standards established by the Society of Interventional Radiology (19). All patients were prescribed a 2-week course of proton pump inhibitors. Patients without diabetes received a 5-day methylpredisolone dose pack to counteract fatigue.

Data Collection and Outcome Measures
All medical, laboratory, and clinical data were prospectively collected. Because use of 90Y microspheres is a liver-directed therapy, tumor response was limited to an assessment of hepatic lesions. Tumor response at CT or MR imaging was determined for a maximum of four measurable lesions (>1 cm) per patient in terms of the product of the greatest cross-sectional tumor length and the length of the corresponding orthogonal projection (cross product). Corresponding lesions from baseline and posttreatment studies were compared during venous and arterial contrast phases to assess tumor morphology and size changes. Complete response was defined as a change in the sum of the cross products to zero (ie, a 100% reduction); partial response, as a decrease in the sum of cross products by at least 50%; stable disease, as a decrease in the sum of cross products by less than 50% or an increase less than 25%; and progression, as an increase in the sum of cross products by at least 25% (20). Posttreatment studies were compared side by side on a computer display with pretreatment images and were assessed simultaneously by three board-certified radiologists (R.S.; R.J.L.; and F.H.M., who had 14 years of experience). The primary end point was survival. Survival was calculated for the entire group and was then stratified by age, tumor vascularity, tumor number, and tumor type. Secondary end points included clinical and laboratory toxicities, as well as tumor response.

Statistical Analysis
All statistical analysis was performed by using software (SAS, version 8.2; SAS Institute, Cary, NC). The treated-patient sample was assessed relative to demographics, functional ECOG performance status, tumor burden, and liver function laboratory measurements before treatment. Median, minimum, and maximum values were used to describe the doses (in grays) delivered to the treated liver, which was categorized by the location (bilobar, right lobe, or left lobe) of tumor burden at presentation. Lung dose (in grays) was accumulated during treatments, which was based on the percentage of activity estimated to flow to the lungs at technetium 99m macroaggregated albumin imaging.

Survival analyses were conducted by using time from the first treatment until death or by censoring at the last follow-up date. Median survival (in days) and corresponding 95% confidence intervals (CIs) were computed by using the Kaplan-Meier method (21). The log-rank statistic was used for statistical significance testing of survival distributions between the various subgroups of patients (22). A P value of less than .05 indicated a significant difference.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Demographics
One hundred thirty-seven patients underwent a total of 225 administrations of 90Y microspheres by using transcatheter intraarterial infusion (Table 1). The median age of patients was 61 years, and there were 66 men and 71 women. Primary sites (origins) of malignancy included colon (n = 51), breast (n = 21), neuroendocrine (n = 19), cholangiocarcinoma (n = 7), pancreas (n = 6), lung (n = 5), melanoma (n = 5), renal (n = 4), esophageal (n = 3), adenocarcinoma unknown primary (n = 3), ovary (n = 2), adrenal (n = 1), angiosarcoma (n = 1), bladder (n = 1), cervical (n = 1), duodenal (n = 1), gallbladder (n = 1), gastric (n = 1), lymphoma (n = 1), parotid (n = 1), squamous cell carcinoma (n = 1), and thyroid (n = 1). All patients were considered to have unresectable disease, and none responded to standard-of-care polychemotherapy (Table 2). All patients' performance status was evaluated by using the ECOG criteria (Table 3). Patients received a mean number of 1.6 treatments (range, 1–6), and all were released from the hospital within 6 hours of the procedure.


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  		Table 1. Patient Demographics and Treatment

 

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  		Table 2. Patient Demographics according to Primary Disease

 

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  		Table 3. ECOG Performance Status in Patients according to Tumor Groups

 
Baseline Imaging Characteristics
Baseline tumor burden before therapy is shown in Table 4. Eighty percent of patients had a tumor burden of 25% or less, 15% had 26%–50% tumor replacement, and 5% had 51%–75% tumor burden. No patients had greater than 76% tumor replacement. The presence of any prior treatments to the liver was also noted. Eighty-four percent of patients had not previously undergone any liver-directed therapies, such as radiofrequency ablation or transarterial chemoembolization. Limited extrahepatic metastases were noted in 50% of all patients. The portal vein was occluded in 4% of patients. Sixty-six percent of patients had more than four liver lesions at their initial evaluation. Forty-four percent of patients had mesenteric anatomy that required some transarterial intervention, such as coil embolization prior to treatment (eg, gastroduodenal, right gastric, falciform, or accessory left gastric artery embolization). Sixty-eight of 137 patients underwent baseline PET.


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  		Table 4. Baseline Imaging Results and Laboratory Characteristics of Patients

 
Tumor Response
A total of 332 lesions in 137 patients were measured. The median number of follow-up studies was two (range, 1–10). The mean imaging follow-up time was 159 days (95% CI: 22, 758). The mean and median lesion size was 4.2 and 2.8 cm, respectively (range, 1.0–16.2 cm). The time to partial response was 133 days (95% CI: 120, 170). A complete response was demonstrated in 2.1% of lesions, and 40.7% of lesions had a partial response, for an overall World Health Organization response rate of 42.8%. Forty-seven percent of lesions had stable disease, and 10.2% had progression according to World Health Organization criteria. When looking at radiologic criteria alone (ie, any decrease in tumor size after treatment), there was an 87% tumor response to treatment and a 13% rate of progression (Figure). The median time to progression was 462 days (95% CI: 422, 541). The median duration of response was 433 days (95% CI: 341, 541). There was a 50% decrease in tumor markers in 20 (37%) of 54 patients with available pre- and posttreatment data. Of the 68 patients with initial PET scans, the response assessment at PET was as follows: complete response, 9; partial response, 52; and progressive disease, 12. Some patients underwent more than one PET scan; however, the overall response rate was 90% (61 of 68 patients).


Figure 1
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  		Waterfall plot demonstrates maximum change from baseline in cross product of 332 lesions after therapy.

 
Safety Assessment
All patients were treated on an outpatient basis and hence released on the same day as treatment. The most common clinical toxicity was fatigue (56%), followed by nonspecific self-limiting abdominal pain (26%), nausea (23%), fever (6%), anorexia (6%), diarrhea (6%), transient gustatory change (1.5%), groin hematoma (1.5%), and chills (1.5%). Of all patients, 89.8% had a normal bilirubin level at baseline, 5.8% had grade 1 bilirubin toxicity, and 4.4% had grade 2 toxicity (Table 5). After treatment, 100 patients (76.3%) showed no change in serum total bilirubin level after therapy. Six patients had grade 3 or 4 bilirubin toxicity; four improved from baseline levels (Table 5). There was no significant difference in bilirubin toxicities on the basis of tumor type. Twenty-nine percent had no clinical complaints after treatment.


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  		Table 5. Bilirubin Toxicity 90 Days after Baseline

 
Follow-up data on lymphocytes was available in 131 patients. Eighty-six (62.8%) patients had a normal lymphocyte count prior to treatment. At follow-up, 44.5% remained unchanged from their preprocedural values. Sixty-eight (49.6%) had a decrease in their lymphocyte counts after treatment (Table 6).


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  		Table 6. Lymphocyte Data

 
Five patients had complications that required subsequent interventions. These were classified as major complications. There was one case of gastrointestinal ulceration (biopsy proved) and one case of radiation-induced cholecystitis requiring surgery. Two patients developed bilomas requiring percutaneous external drainage. One patient with previous hepaticojejunostomy developed a hepatic abscess requiring external drainage.

Treatment Dosimetry
The median volume of the treated lobes was 840 cm3 (range, 250–2700 cm3). The median activity at the time of infusion in the dose vial was 1.83 GBq (range, 0.7–6.9 GBq). The median residual activity in the vial was 1.8% (0%–30.7%). The median lung shunt fraction was 3.7% (range, 0%–26.6%). The median lung dose was 3.18 Gy. The mean radiation absorbed dose per site was 112.8 Gy (range, 27–180 Gy) (Table 7).


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  		Table 7. Yttrium 90 Dosing Parameters

 
Survival
Seventy (51.1%) patients died during follow-up (Table 8). Mean clinical follow-up was 287 days. The median survival for all patients was 300 days (95% CI: 234, 591). The 1-year survival rate for the group was 47.8%, and 2-year survival rate was 30.9%. Fifty-five percent of patients were younger than 65 at initial treatment. The median survival rate for those younger than 65 was 255 days, compared with 591 days for those older than 65 years old. Patients with hypervascular tumors at angiography had a median survival time of 300 days, whereas those with hypovascular tumors had a median survival of 261 days. Similarly, patients with tumors that were hypervascular at cross-sectional imaging had a median survival of 306 days, compared with 284 days for those with hypovascular tumors. Patients with four or fewer lesions had a median survival rate of 632 days, but those with more than four lesions had a median survival rate of 234 days. A subset analysis of colorectal, neuroendocrine, and noncolorectal, nonneuroendocrine tumors in patients demonstrated median survival rates of 457 (15.2 months), 776 (25.9 months), and 207 (6.9 months) days, respectively.


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  		Table 8. Survival Analysis

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
A large number of patients with metastatic disease of the liver either initially do not respond to systemic chemotherapy or ultimately have disease that becomes chemorefractory. For these patients, liver-directed therapies aimed at treating liver metastases directly provide an effective alternative. The purpose of this open-label phase II study was to assess the safety and efficacy of radioembolization in this patient population.

The number of men and women in our cohort was similar, as was the number of patients younger than age 65 and those 65 and older. Half the patients received only one treatment, while the remainder required multiple radioembolizations. Given that the therapy used has been shown to be minimally embolic, multiple repeated treatments through the same artery are possible given the preserved vascular patency (23). This is because the end point of this therapy is not complete macrovascular occlusion and embolization. Rather, the primary modes of action of this therapy are tissue radiation, not tissue ischemia, and microvascular embolization without reaching stasis.

Radioembolization with this therapy has been shown to be clinically well tolerated (1,4,24). Our study results confirm this finding because only two patients experienced the major complications of radiation cholecystitis and ulceration. Clinically, the most common complaints were fatigue, pain, and nausea. Almost 30% of patients had no complaints after treatment. Patients were all treated on a same-day basis with minimal restrictions after the procedure. In the majority of patients (76.3%), there was no change in serum bilirubin level at 90 days. Seven patients had grade 3 or 4 bilirubin toxicity; all of these toxicities were attributed to disease progression. Four patients actually had an improvement in their bilirubin toxicities after treatment. One possible explanation for this phenomenon is that the initial elevated bilirubin level was caused by mild biliary compression by the tumor, resulting in obstruction. After treatment, a decrease in tumor size may result in improvement of the microscopic obstruction. In 44.3% of patients, there was no change in the lymphocyte count from preprocedural levels; however, 49.6% decreased from normal levels. Despite this lymphopenia, this finding was of no clinical consequence, because no patients had signs or symptoms of opportunistic infections.

Tumors treated had a mean diameter of 4.2 cm. Median time to partial response was 133 days. This is slightly longer than previous reports of 75–82 days with this therapy (25,26). Overall, there was a response rate of 42.8% at the lesional level (2.1% complete response, 40.7% partial response). However, because the World Health Organization criteria for response require at least a 50% decrease in size of the lesion, many tumors that had a radiologic response were still classified as stable disease. The actual biologic response rate of treated tumors was 87%, with those lesions showing at least some decrease in size after therapy. Although the progression rate for this group was 10.2% by using World Health Organization criteria, the actual radiologic progression rate was 13% (any increase in size). Functional response rate was supported by the 90% response at PET observed in this cohort of patients. Twenty (37%) of 54 patients had a 50% decrease in tumor marker levels after treatment.

Differences in survival were seen with different tumor type, ECOG performance status, tumor burden, imaging findings (hypovascular or hypervascular tumors at angiography and cross-sectional imaging), and number of tumors. Median survival rate for patients with colorectal cancer, neuroendocrine tumors, and noncolorectal, nonneuroendocrine tumors were 457, 776, and 207 days, respectively. This subset analysis into three categories has set the stage for further investigation in these patient cohorts.

Patients with an ECOG performance status of 0 had a median survival time of 731 days, while those with an ECOG performance status of more than 0 had a median survival of 137 days. This trend was maintained across all tumor types and reached statistical significance, supporting the notion of poor prognosis once cancer-related symptoms appear (ECOG > 0). A similar phenomenon was noted with stratification according to tumor burden. Patients with greater tumor burden appear to have a significantly lower survival rate than patients with a tumor burden of 0%–25% (506 days). Not surprisingly, this difference was also maintained for patients with colorectal cancer but not for those with neuroendocrine tumors or other tumor types. Patients with neuroendocrine tumors classically have prolonged survival rates despite significant disease burden.

At cross-sectional imaging, 82.5% of patients had hypovascular lesions in the liver, while at angiography 78.8% of tumors appeared hypervascular. All patients were treated in the same manner, and there was no significant difference in the median survival rate or the 1- and 2-year survival rates. Patients with hypervascular tumors at angiography had a median survival time of 300 days, whereas those with hypovascular tumors had a median survival of 261 days. Similarly, patients with tumors that were hypervascular at cross-sectional imaging had a median survival time of 306 days, compared with 284 days for those with hypovascular tumors. These findings suggest the following: (a) significant discrepancy exists in the perceived vascularity of liver metastases as assessed at cross-sectional imaging compared with that at the reference standard (angiography) and (b) the degree of vascularity is not predictive of survival. This implies that the radiologic appearance of tumors may not affect the delivery of microspheres and should not be used to include or exclude patients for this type of therapy. A statistically worse survival rate was noted in patients with more than four liver lesions (234 days) compared with those with four or fewer (632 days), a finding consistent with the surgical literature for colorectal cancer.

There were limitations to our study. First, this is a heterogeneous cohort treated and observed longitudinally without a true comparator arm. However, given that these are patients with chemorefractory disease who have previously not responded to standard-of-care therapies, no such control arm exists. The closest comparison of patients who did not respond to systemic therapy and were treated with supportive care demonstrated an overall survival of 6 months (27). Second, many of these patients were treated prior to the clinical availability of growth factor inhibitors, which made the impact of new chemotherapeutic agents difficult to assess. Third, this was an open-label phase II study with a heterogeneous population, which limits the ability to generalize the findings. However, surgical treatment in similarly heterogeneous patients has been previously reported to be beneficial (28–31). For radioembolization, subset analyses of these data are now being used to identify specific patients who might definitively benefit from this treatment. This study was performed at two institutions and warrants independent validation.

In conclusion, radioembolization represents a treatment option in patients with chemorefractory liver metastases. This therapy was able to halt or reverse progression at imaging in 87% of lesions with acceptable toxicity. Functional response was 90% at PET. Our study results suggest that radioembolization may benefit patients with chemorefractory liver metastases and may potentially affect overall or progression-free survival compared with that of supportive care. Given the demonstration of anatomic and functional response confirming tumoricidal effects from radioembolization, controlled studies in specific patient subsets in combination with chemotherapeutics or biologics are now being initiated.


   ADVANCE IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   ACKNOWLEDGMENTS
 
The authors thank Suzanne Hackett, MS, and the team from StatWorks (Carrboro, NC) for managing the data and validating its integrity.


   FOOTNOTES
 

Abbreviations: CI = confidence interval • ECOG = Eastern Cooperative Oncology Group

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantor of integrity of entire study, R.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, K.T.S., R.J.L., M.F.M., B.A., A.A.N., C.Y.O.W., K.G.T., R.S.; clinical studies, K.T.S., R.J.L., M.F.M., B.A., R.K.R., V.L.G., O.B., R.M., M.T., C.Y.O.W., F.H.M., S.B.N., J.M.S., R.A.O., R.S.; statistical analysis, R.J.L., M.F.M., B.A., R.A.O., R.S.; and manuscript editing, R.J.L., B.A., R.K.R., A.B., F.H.M., K.G.T., R.A.O., R.S.

Clinical trial registration no. NCT00532740 [ClinicalTrials.gov] .


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCE IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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