Lung Shunt Fraction Research Articles

Abstract No. 421 Role of technetium-99m lung shunt fraction studies for the detection of primary recanalization after pulmonary avm embolization in patients with hereditary hemorrhagic telangiectasia (HHT)

To determine the utility of nuclear medicine technetium-99m lung shunt fraction studies in identifying primary recanalization of embolized pulmonary AVMs in patients with HHT. We retrospectively identified all HHT patients with treated pAVMs between January 2000 and August 2017. Only pulmonary AVMs with no prior treatment and patients with both clinical and imaging follow-up were included. Imaging follow-up required a pre- and postprocedure technetium-99m lung shunt fraction study and another imaging study that could evaluate for recanalization such as a contrast-enhanced CT Chest or pulmonary angiogram. Ninety-two pulmonary AVMs (pAVMs) met the above criteria and were embolized with coils or plugs in 27 patients with HHT in 35 separate cases. The patients consisted of 9 males (33%) and 18 females (66%) with an average age of 56 (range, 26-81). Treatment included Nester coils only (n = 35, 38%), Tornado only (n = 20,22%), combination of Nester and Tornado coils (n = 31,34%), amplatzer plug (n = 3, 3%), and other coils (Hilal-Silver and Ruby) (n = 3, 3%). Technical success was achieved in all cases. Mean follow-up was 5.2 years (range, 0.1-12.2). There were 8 (8.7%) pAVMs that demonstrated primary recanalization as determined by a contrast-enhanced CT chest or pulmonary angiogram. The shunt fraction increased in the recanalization group by 2.2% (range, -3.4 to 9.1) versus a reduction of 3.1% (range, -19.1 to -9.1) in the non-recanalization group. Statistical analysis using univariate analysis demonstrated significant difference (p = 0.0195) between the two groups. There was a significant shunt fraction difference between the treated pAVMs that recanalized and those with durable treatment, specifically the recanalized group had a mean increase in their post procedural pulmonary shunt. As such, technetium-99m lung shunt fraction studies may be useful in surveillance of embolized pAVMs in patients with HHT. Furthermore, technetium-99m lung shunt fraction studies may serve as a viable option for follow-up in patients with contraindications to a CT chest with iodinated contrast or a pulmonary angiogram.

3:27 PM Abstract No. 274 A prospective study of lung shunt fraction as a determinant of DEB-TACE response and metastasis and determinants of lung shunt fraction

3:27 PM Abstract No. 274 A prospective study of lung shunt fraction as a determinant of DEB-TACE response and metastasis and determinants of lung shunt fraction

Abstract No. 550 Hepatic vein invasion is associated with a higher lung shunt fraction than portal vein invasion

Abstract No. 550 Hepatic vein invasion is associated with a higher lung shunt fraction than portal vein invasion

A Prospective Study of Quantitative SPECT/CT for Evaluation of Lung Shunt Fraction Before SIRT of Liver Tumors

The lung shunt fraction (LSF) is estimated using 99mTc-macroaggregated albumin (99mTc-MAA) imaging before selective internal radiotherapy (SIRT) of the liver to reduce the risk of pulmonary irradiation. Generally, planar scans are acquired after injection of 99mTc-MAA into the hepatic artery. However, the validity of this approach is limited by differences in attenuation between liver and lung tissue as well as inaccurate segmentation of the organs. The aim of this study was to evaluate quantitative SPECT/CT for LSF assessment in a prospective clinical cohort. Methods: Fifty consecutive patients intended to undergo SIRT were imaged within 1 h after injection of 99mTc-MAA using a SPECT/CT γ-camera. Planar scans of the lung and liver region were acquired in anterior and posterior views, followed by SPECT/CT scans of the thorax and abdomen. Emission data were corrected for scatter, attenuation, and resolution recovery using dedicated software. To quantify the radioactivity concentration in the lung, liver, urinary bladder and remainder of the thoracoabdominal body, volumes of interest were defined on the SPECT/CT images. 99mTc-MAA concentrations were calculated as percentage injected dose (%ID). Results: Mean 99mTc-MAA uptake in liver and lung accounted for only 79 %ID, whereas 13.1 %ID was present in the remainder of the body. In all patients, LSF as calculated from planar scans accounted for a median of 6.8% (range, 3.4%-32.3%), whereas the SPECT/CT quantitation revealed significantly lower LSF estimates, at a median of 1.9% (range, 0.8%-15.7%) (P < 0.0001, Wilcoxon test). On the basis of planar imaging, dose reduction or even contraindications to SIRT had to be considered in 10 of 50 patients, as their LSF was calculated at 10% or more. In contrast, SPECT/CT quantitation showed substantial shunting in only 2 of the 50 patients. Conclusion: Quantitative SPECT/CT reveals that the LSF is considerably lower than shown on planar imaging. Thus, the resulting dose to the lung parenchyma may be less than conventionally assumed. However, the safety of the SPECT/CT-derived dose range will have to be evaluated.

The effect of selective internal radiation therapy with yttrium-90 resin microspheres on lung carbon monoxide diffusion capacity

BackgroundSelective internal radiation therapy (SIRT) with embolization of branches of the hepatic artery is a valuable therapeutic tool for patients with hepatic malignancies; however, it is also associated with lung injury risk due to shunting. Diffusion capacity of the lungs for carbon monoxide (DLCO) is a clinically significant lung function test, and worsening in DLCO is suggested to reflect a limited gas exchange reserve caused by the potential toxicity of chemoradiotherapy or it may be a marker of related lung injury. This study aimed to examine the changes in DLCO during SIRT with resin microspheres in newly treated and retreated patients. Forty consecutive patients who received SIRT for a variety of malignant conditions were included. All subjects were treated with Yttrium-90 labelled resin microspheres. DLCO tests were performed after the procedures. In addition, patients were specifically followed for radiation pneumonitis.ResultsThe mean DLCO did not significantly change after the first (82.8 ± 19.4 vs. 83.1 ± 20.9, p = 0.921) and the second treatments (87.4 ± 19.7 vs. 88.6 ± 23.2, p = 0.256). Proportion of patients with impaired DLCO at baseline was not altered significantly after the first (37.5 vs. 45.0%, p = 0.581) and the second treatments (27.3 vs. 27.3%, p = 1.000). Also, percent change in DLCO values did not correlate with radiation dose, lung shunt fraction, or lung exposure dose (p > 0.05 for all comparisons). None of the patients developed radiation pneumonitis.ConclusionsOur results suggest that no significant change in DLCO in association with SIRT occurs, both after the first or the second treatment sessions. Further larger studies possibly with different protocols are warranted to better delineate DLCO changes after SIRT in a larger spectrum of patients.

Estimation of lung shunt fraction from simultaneous fluoroscopic and nuclear images

Radioembolisation with yttrium-90 (90Y) is increasingly used as a treatment of unresectable liver malignancies. For safety, a scout dose of technetium-99m macroaggregated albumin (99mTc-MAA) is used prior to the delivery of the therapeutic activity to mimic the deposition of 90Y. One-day procedures are currently limited by the lack of nuclear images in the intervention room. To cope with this limitation, an interventional simultaneous fluoroscopic and nuclear imaging device is currently being developed. The purpose of this simulation study was to evaluate the accuracy of estimating the lung shunt fraction (LSF) of the scout dose in the intervention room with this device and compare it against current clinical methods. Methods: A male and female XCAT phantom, both with two respiratory profiles, were used to simulate various LSFs resulting from a scout dose of 150 MBq 99mTc-MAA. Hybrid images were Monte Carlo simulated for breath-hold (5 s) and dynamic breathing (10 frames of 0.5 s) acquisitions. Nuclear images were corrected for attenuation with the fluoroscopic image and for organ overlap effects using a pre-treatment CT-scan. For comparison purposes, planar scintigraphy and mobile gamma camera images (both 300 s acquisition time) were simulated. Estimated LSFs were evaluated for all methods and compared to the phantom ground truth. Results: In the clinically relevant range of 10–20% LSF, hybrid imaging overestimated LSF with approximately 2 percentage points (pp) and 3 pp for the normal and irregular breathing phantoms, respectively. After organ overlap correction, LSF was estimated with a more constant error. Errors in planar scintigraphy and mobile gamma camera imaging were more dependent on LSF, body shape and breathing profile. Conclusion: LSF can be estimated with a constant minor error with a hybrid imaging device. Estimated LSF is highly dependent on true LSF, body shape and breathing pattern when estimated with current clinical methods. The hybrid imaging device is capable of accurately estimating LSF within a few seconds in an interventional setting.

Is a Technetium-99m Macroaggregated Albumin Scan Essential in the Workup for Selective Internal Radiation Therapy with Yttrium-90? An Analysis of 532 Patients

PurposeTo determine if baseline patient, tumor, and pretreatment evaluation characteristics could help identify patients who require technetium-99m (99mTc) macroaggregated albumin (99mTc MAA) imaging before selective internal radiation therapy (SIRT). Materials and MethodsIn this retrospective analysis, 532 consecutive patients with primary (n = 248) or metastatic (n = 284) liver tumors were evaluated between 2006 and 2015. Variables were compared between patients in whom 99mTc MAA imaging results contraindicated/modified SIRT administration with yttrium-90 (90Y) resin microspheres and those who were treated as initially planned. The 99mTc MAA findings that contraindicated/modified SIRT were a lung shunt fraction (LSF) > 20%, gastrointestinal 99mTc MAA uptake, or a mismatch between 99mTc MAA uptake and intrahepatic tumor distribution. ResultsLSF > 20% and gastrointestinal MAA uptake were observed in 7.5% and 3.9% of patients, respectively, and 11% presented a mismatch. Presence of a single lesion (odds ratio [OR] = 2.4) and vascular invasion (OR = 5.5) predicted LSF > 20%, and GI MAA uptake was predicted by the presence of liver metastases (OR = 3.7) and 99mTc MAA injection through the common/proper hepatic artery (OR = 4.7). Vascular invasion (OR = 4.1) was the only predictor of LSF > 20% and/or GI MAA uptake (sensitivity = 49.2%, specificity = 80.3%, negative predictive value = 92.4%). Previous antiangiogenic treatment (OR = 2.4) and presence of a single lesion (OR = 2.6) predicted mismatch. ConclusionsImaging with 99mTc MAA is essential in SIRT workup because baseline characteristics may not adequately predict 99mTc MAA results. Nevertheless, the absence of vascular invasion potentially identifies a group of patients at low risk of SIRT contraindication/modification in whom performing SIRT in a single session (ie, pretreatment evaluation and SIRT on the same day) should be explored.

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Radioembolization of Colorectal Liver Metastases: Indications, Technique, and Outcomes.

Liver metastases are a major cause of death from colorectal cancer. Intraarterial therapy options for colorectal liver metastases include chemoinfusion via a hepatic arterial pump or port, irinotecan-loaded drug-eluting beads, and radioembolization using 90Y microspheres. Intraarterial therapy allows the delivery of a high dose of chemotherapy or radiation into liver tumors while minimizing the impact on liver parenchyma and avoiding systemic effects. Specificity in intraarterial therapy can be achieved both through preferential arterial flow to the tumor and through selective catheter positioning. In this review, we discuss indications, contraindications, preprocedure evaluation, activity prescription, follow-up, outcomes, and complications of radioembolization of colorectal liver metastases. Methods for preventing off-target embolization, increasing the specificity of microsphere delivery, and reducing the lung-shunt fraction are discussed. There are 2 types of 90Y microspheres: resin and glass. Because glass microspheres have a higher activity per particle, they can deliver a particular radiation dose with fewer particles, likely reducing embolic effects. Glass microspheres thus may be more suitable when early stasis or reflux is a concern, in the setting of hepatocellular carcinoma with portal vein invasion, and for radiation segmentectomy. Because resin microspheres have a lower activity per particle, more particles are needed to deliver a particular radiation dose. Resin microspheres thus may be preferable for larger tumors and those with high arterial flow. In addition, resin microspheres have been approved by the U.S. Food and Drug Administration for colorectal liver metastases, whereas institutional review board approval is required before glass microspheres can be used under a compassionate-use or research protocol. Finally, radiation segmentectomy involves delivering a calculated lobar activity of 90Y microspheres selectively to treat a tumor involving 1 or 2 liver segments. This technique administers a very high radiation dose and effectively causes the ablation of tumors that are too large or are in a location considered unsafe for thermal ablation. The selective delivery spares surrounding normal liver, reducing the risk of liver failure.

Impact of respiratory motion and acquisition settings on SPECT liver dosimetry for radioembolization.

Respiratory motion may impose significant inaccuracies on emission activity estimation in quantitative SPECT. This effect may be a major issue in dosimetry as used in the management of liver radioembolization. The purpose of this study was to investigate the impact of respiratory motion on radioembolization liver dosimetry for different SPECT acquisition settings. In a series of SPECT/CT Monte Carlo simulations using several digital XCAT phantoms, the following parameters were varied: breathing/nonbreathing, liver tumor size (0.3-35 ml) and location, patient properties (body mass index ranging from underweight to obese; male and female), acquisition time (10-30 s/view), collimator setup (High Sensitivity, High Resolution, Ultra High Resolution) and tumor VOI. The effect of applying a respiratory gating scheme was examined as well. Breathing decreased activity recovery and tumor/non-tumor (T/N) ratios on average from 90% to 66%. VOIs based on SPECT images instead of breath-hold CT improved T/N values significantly. The most accurate results were obtained using a gating scheme combined with SPECT-based VOIs. Scan duration, body mass index, sex, and location all had a minor effect. Lung shunt fraction estimations were relatively unaffected by any of the varied parameters. Respiratory motion has a large effect on SPECT activity quantitation of liver tumors as used in radioembolization treatment planning and assessment. As compared with the other parameters that were varied in this study, respiration is the predominant degrading effect on image quantitation. Gating alleviates much of this detrimental effect.

Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

The Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) study was a retrospective analysis of 606 patients with unresectable colorectal liver metastases treated with radioembolization (RE) using 90Y-labeled resin microspheres. The first analysis of this study was completed with a last patient follow-up of 77.7 months. We now provide an updated survival analysis through September 15, 2016, with a last patient follow-up of 125 months. 90Y-RE was considered for patients with advanced liver-only or liver-dominant metastatic colorectal cancer which was deemed not suitable for surgery, ablation, or systemic therapy, and which had progressed or become refractory to at least one line of systemic therapy. All patients with a diagnosis of metastatic colorectal cancer who had received at least 1 RE treatment and 1 follow-up visit were included in the analysis. Patients were treated between July 2002 and December 2011 at one of 11 U.S. tertiary care centers. Data were collected at baseline, on the day of the first 90Y-RE treatment (day 0), and at all subsequent visits or until death. Patient medical charts and/or public records were accessed to obtain dates of death. Dates of death were obtained for 574 out of a total of 606 patients, and overall survival (OS) data analyzed. Updated median OS was 10.0 months (95% CI: 9.2-11.8 months) at a median follow-up of 9.5 months versus the originally reported median OS of 9.6 months (95% CI: 9.0-11.1 months) at a follow-up of 8.6 months in the first MORE analysis. Patients received a median (range) of 2 (0 to 6) lines of chemotherapy. Baseline characteristics and factors significantly associated with patient survival (P<0.01) are consistent with those reported in the first safety analysis of the MORE study. These factors include poor ECOG performance status, markers of advanced disease such as increased extent of tumor-to-target liver involvement, poor baseline liver function, pre-treatment anemia, lung shunt fraction, and number of lines of prior chemotherapy. Patient age did not significantly affect survival outcomes. Long-term follow-up confirms that 90Y-RE treatment offers favorable survival benefits for patients with unresectable metastatic colorectal cancer, even among patients who received 3 or more prior lines of chemotherapy. Our analysis also supports earlier reported prognostic factors for survival after 90Y-RE. Overall, our updated analysis confirms that 90Y-RE treatment provided a meaningful response and survival advantage for MORE patients across all ages and across diverse community and academic centers in the U.S.

Safety analysis of regorafenib prior to selective internal radiation therapy (SIRT) using 90Y resin microspheres for the treatment (tx) of patients (pts) with refractory metastatic colorectal cancer (mCRC) with liver metastases (mets).

e15040 Background: SIRT (or radioembolization) has been successfully used in the tx of mCRC patients with liver mets who are not surgical candidates. The addition of the multi-kinase inhibitor, regorafenib to SIRT is an attractive option as anti-tumor and maintenance tx for refractory CRC. Here we present the safety analysis of the 1st of 2 cohorts of our Phase II, open-label study comparing the safety of the combination of SIRT and regorafenib where chemotherapy occurs either before or after SIRT. Methods: mCRC pts with evidence of liver mets not treatable by surgical resection or local ablation were tx with 160 mg regorafenib QD PO on days 1-21 of a 28-day cycle followed by a 1 week (wk) washout then SIRT infusion (SIR-Spheres; Sirtex, North Sydney, Australia). Liver function was evaluated 2 wks and 4 wks after SIRT, and regorafenib was re-initiated if liver function was normal. Pts were evaluated for safety, and restaged on wk 6 and 12 following SIRT. The primary objective was to evaluate the safety of this tx schema. Results: 25 pts were enrolled from 7/15 to 8/16: median age 56 yrs, 48% male; 88% colon cancer, 12%, rectal cancer; 48% KRASmt, 4% BRAFmt. 68% of pts had prior systemic therapy for metastatic disease and 80% of pts had prior CRC surgeries. Pts received a median 11 wks regorafenib. 3 pts received regorafenib, but not SIRT due to disease progression. The median activity of SIRT delivered to the liver was 38 mCi and the median lung shunt fraction was 4%. The median tumor volume treated was 76 mL. The most common tx-related adverse events (AEs) were fatigue (60% all grades [G]; 8% G3/4), decreased appetite (32% all G; 0 G 3/4), and nausea (32%, all G; G 3/4). There were 4 tx-related serious AEs (bowel perforation, intractable abdominal pain, portal hypertension, and diarrhea) and no tx-related deaths. The overall response rate was 4%. The median PFS was 4 months and the median OS was 12 months. Conclusions: The treatment of mCRC pts with liver mets with regorafenib followed by SIRT infusion was found to be tolerable in this pt population. Further efficacy analysis of this treatment schema is merited. Clinical trial information: NCT02195011.

Indicators of Lung Shunt Fraction Determined by Technetium-99m Macroaggregated Albumin in Patients with Hepatocellular Carcinoma.

To determine the correlation of pre-procedural and imaging characteristics with lung shunt fraction (LSF) measured by technetium-99m macroaggregated albumin (99mTc-MAA) scan in patients with hepatocellular carcinoma. A retrospective study was conducted of 428 subjects with hepatocellular carcinoma from 2004 to 2011 assessed for lung shunting by 99mTc-MAA scan. Baseline characteristics included age, gender, ethnicity, tumor burden, maximum dimension, number of lesions, presence of extrahepatic metastases, macrovascular (hepatic and portal vein) invasion, ascites on imaging, laboratory values, and alpha-fetoprotein (AFP). Univariate and multivariate logistic regression analysis was performed. Receiver operating characteristic curves were used to obtain sensitivity (SN), specificity (SP), and positive likelihood ratios (LR+) of characteristics for low LSF (LSF <10%) and high LSF (LSF >20%). Statistically significant (p<0.05) independent indicators of low LSF included bilirubin <1.45mg/dL (SN=49.5%, SP=69.1%, LR+=1.60), maximum tumor size <7.15cm (SN=66.0%, SP=75.9%, LR+=2.74), AFP ≤200ng/mL (SN=64.6%, SP=65.0%, LR+=1.85), and absent macrovascular invasion (SN=73.9%, SP=64.9%, LR+=2.11). Independent indicators of high LSF included albumin <2.65g/dL (SN=64.3%, SP=64.1%, LR+=1.79) and macrovascular invasion (SN=74.4%, SP=67.4%, LR+=2.28). A combined risk factor model was constructed. If there is no macrovascular invasion: [Formula: see text]. With macrovascular invasion, [Formula: see text] (R 2=0.257). Since these factors all have LR+ between 2 and 5, they only reflect slight increase in LSF predictivity. Serum AFP, albumin, bilirubin, and portal/hepatic vein invasion on cross-sectional imaging are statistically significant but weak clinical indicators of LSF, as shown by low SN, SP, and LR+ for clinically relevant cutoff LSF values. Thus, these factors cannot be relied upon in clinical practice.

Hepatopulmonary Shunting: A Prognostic Indicator of Survival in Patients with Metastatic Colorectal Adenocarcinoma Treated with 90Y Radioembolization.

Purpose To determine if high lung shunt fraction (LSF) is an independent prognostic indicator of poor survival in patients who undergo yttrium 90 radioembolization for unresectable liver-dominant metastatic colorectal cancer. Materials and Methods Retrospective data were analyzed from 606 patients (62% men; mean age, 62 years) who underwent radioembolization to treat liver metastases from colorectal adenocarcinoma between July 2002 and December 2011 at 11 U.S. centers. Institutional review board exemptions were granted prior to the collection of data at each site. Overall survival was estimated by using Kaplan-Meier survival and univariate Cox proportional hazards models to examine the effect of LSF on survival and to compare this to other potential prognostic indicators. Multivariate analysis was also performed to determine whether LSF is an independent risk factor for poor survival. Results LSF higher than 10% was predictive of significantly decreased survival (median, 6.9 months vs 10.0 months; hazard ratio, 1.60; P < .001) and demonstrated a mild but significant correlation to serum carcinoembryonic antigen levels and tumor-to-liver volume ratio (Pearson correlation coefficients, 0.105 and 0.113, respectively; P < .05). A progressive decrease in survival was observed as LSF increased from less than 5% to more than 20% (P < .05). LSF did not correlate with the presence of extrahepatic metastases or prior administration of bevacizumab. Conclusion Increased LSF is an independent prognostic indicator of worse survival in patients undergoing radioembolization for liver-dominant metastatic colorectal adenocarcinoma. High LSF correlates poorly to other potential markers of tumor size, such as tumor-to-liver volume ratio or serum carcinoembryonic antigen level, and does not correlate to the presence of extrahepatic metastases. © RSNA, 2016 Online supplemental material is available for this article.

SU-F-T-687: Comparison of SPECT/CT-Based Methodologies for Estimating Lung Dose from Y-90 Radioembolization

Purpose: To compare mean lung dose (MLD) estimates from 99mTc macroaggregated albumin (MAA) SPECT/CT using two published methodologies for patients treated with 90Y radioembolization for liver cancer. Methods: MLD was estimated retrospectively using two methodologies for 40 patients from SPECT/CT images of 99mTc-MAA administered prior to radioembolization. In these two methods, lung shunt fractions (LSFs) were calculated as the ratio of scanned lung activity to the activity in the entire scan volume or to the sum of activity in the lung and liver respectively. Misregistration of liver activity into the lungs during SPECT acquisition was overcome by excluding lung counts within either 2 or 1.5 cm of the diaphragm apex respectively. Patient lung density was assumed to be 0.3 g/cm3 or derived from CT densitovolumetry respectively. Results from both approaches were compared to MLD determined by planar scintigraphy (PS). The effect of patient size on the difference between MLD from PS and SPECT/CT was also investigated. Results: Lung density from CT densitovolumetry is not different from the reference density (p = 0.68). The second method resulted in lung dose of an average 1.5 times larger lung dose compared to the first method; however the difference between the means of the two estimates was not significant (p = 0.07). Lung dose from both methods were statistically different from those estimated from 2D PS (p 0.17). Conclusion: There is no statistically significant difference between MLD estimated from the two techniques. Both methods are statistically different from conventional PS, with PS overestimating dose by a factor of three or larger. The difference between lung doses estimated from 2D planar or 3D SPECT/CT is not dependent on patient size.

Role of yttrium-90 in the management of unresectable hepatocellular carcinoma and hepatic metastases.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The management of unresectable HCC and hepatic metastases from various solid tumors is a clinical dilemma. There is paucity of data on the treatment of unresectable HCC and hepatic metastases with yttrium-90 (90Y) radioembolization. Thirty patients (mean age; 55.2years; range 43-82years) comprising 21 patients with HCC (12 patients have cirrhosis of which 3 patients belong to Child-Pugh class A and 9 patients belong to Child-Pugh class B), 7 patients with metastasis from colorectal cancer, 1 patient with metastasis from melanoma, and 1 patient with metastasis from ovarian carcinoma underwent resin-based 90Y radioembolization between 2013 and 2015 in our study. In all the patients, after embolization of non-target vasculature, SPECT and planar scintigraphy were done with the injection of 5-6mCi (185-222MBq) of 99mTc-labeled macroaggregated albumin (MAA) into the hepatic artery. Then, lung shunt fraction was assessed and dose was calculated based on body surface area (BSA) method for SIR-Spheres. Post therapeutic 90Y bremsstrahlung SPECT and 90Y PET was performed within 30 hours following therapy to see the hepatic and extrahepatic distribution of spheres. Side effects following therapy were noted in all the patients. All patients were followed up with triphasic CT liver 3months following therapy. Therapeutic response was evaluated with necrosis criteria used for therapy response assessment in solid tumors. On follow up, 14 patients (46%) developed minor side effects following treatment and resolved without active intervention. The most common side effects include mild abdominal pain in 11 patients (36%), nausea in 8 patients (26%), and fatigue in 6 patients (20%). On follow up imaging at 3months following treatment, a complete response was observed in two patients (7%), partial response in seven patients (23%), stable disease in 15 patients (50%), and progressive disease in six patients (20%). This study provides supportive evidence of the safety and efficacy on 90Y radioembolization for the treatment of unresectable HCC and hepatic metastases from various solid tumors. 90Y PET is a better radionuclide technique for assessing the hepatic and extrahepatic distribution of spheres following therapy compared to 90Y Bremsstrahlung SPECT. Thus, 90Y radioembolization is proving to be promising treatment with average disease control rates around 80% and should be widely utilized.

Elevated Lung Shunt Fraction as a Prognostic Indicator for Disease Progression and Metastasis in Hepatocellular Carcinoma

PurposeTo evaluate lung shunt fraction (LSF) as an early predictor for local disease progression or the development of metastatic disease. Materials and MethodsRetrospective analysis was performed on 52 patients with hepatocellular carcinoma who underwent preradioembolization assessment, including the calculation of LSF. Comparison of preprocedural and postprocedural surveillance imaging was performed. Mean patient age was 67 years (range, 50–88 y), with a mean surveillance of 245 days (range, 24–871 d). Statistical analysis was conducted to assess the relationship between LSF and local disease progression or development of new metastatic disease. ResultsIn patients in whom metastatic disease developed during routine surveillance, the mean LSF was almost double that in patients in whom no metastasis developed (18.3% vs 9.3%; P = .001). Patients with elevated LSFs were also more likely to show intrahepatic disease progression (15.6% vs 8.5%; P = .003). LSFs < 8% corresponded to negative predictive values of 74% for local disease progression and 95% for development of metastasis, signaling a better prognosis. Of pretreatment variables examined (age, sex, previous treatment with disease progression, lesion size, lesion number, LSF, α-fetoprotein level, and portal vein thrombus), only LSF was an independent predictor for new metastasis (odds ratio [OR] = 1.2; P = .01). LSF (OR = 1.2; P = .03) and progression after previous treatment (OR = 4.7; P = .04) were independent predictors for local progression. ConclusionsAs local disease progression and metastatic disease were more likely to occur in patients with elevated LSFs, LSF may be the most sensitive predictor for local disease progression and new metastatic disease.

Lung Shunt Fraction prior to Yttrium-90 Radioembolization Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis.

To investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival. A single-center, prospective study of 44 consecutive patients (median age: 58.5years, 29.5% male) diagnosed with pancreatic (52.3%) or carcinoid (47.7%) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients' baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10%) and low (<10%) LSF. Baseline comparisons were performed using Fisher's exact tests for categorical and Mann-Whitney U test for continuous variables. Survival was calculated using the Kaplan-Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed. There was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n=15) and low (n=29) LSF. The median OS was 27.4months (95%CI 12.73-55.23), with 4.77months (95%CI 2.87-26.73) for high and 42.77months (95%CI 18.47-59.73) for low LSF (p=0.003). Multivariate analysis identified high LSF (p=0.001), total serum bilirubin >1.2mg (p=0.016), and lack of pretreatment with octreotide (p=0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival. LSF ≥10%, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

3:18 PMAbstract No. 141 - Risk factors for high lung shunt fraction in patients with hepatocellular carcinoma being evaluated for yttrium-90 radioembolization

3:18 PMAbstract No. 141 - Risk factors for high lung shunt fraction in patients with hepatocellular carcinoma being evaluated for yttrium-90 radioembolization

Use of yttrium-90 radioembolization for patients with unresectable liver metastases: experience from a single center

Background: Yttrium-90 (Y-90) radioembolization is an intra-arterial, catheter-based therapy that delivers high doses of internal radiation to tumors while sparing normal surrounding tissue. Metastatic liver disease, in general, is associated with a poor prognosis from a variety of primary gastrointestinal malignancies. As a result, Y-90 radioembolization has an emerging role in locoregional control of patients with unresectable liver metastases. Methods: Patients with cancer that metastasized to the liver and treated with Y-90 radioembolization between 2005 and 2015 (n=21) were evaluated retrospectively. Patients were selected based on multidisciplinary evaluation; inclusion criteria included data that were abstracted from medical records including patient records, laboratory data, and radiographic studies. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to mRECIST criteria. Results: Twenty-one patients received treatments with SIR-Spheres Y-90 radioembolization. The median treatment activity delivered was 1.3 gBq (range, 0.7–1.7 gBq). The median treatment dose delivered was 95.5 Gy (range, 50–120 Gy). The median lung shunt fraction was 2.0% (range, 0.5–5.8%). Toxicities as measured by laboratory values were overall low, with alkaline phosphatase (Alk Phos) being most commonly elevated following treatment in 52% of patients, followed by AST and ALT derangements in 29% and 33% of patients, respectively. The most common clinical toxicities among all patients were abdominal pain (43%), followed by nausea/vomiting (38%), fatigue (19%), anorexia (14%), and diarrhea (10%). A clinical benefit response was seen in 71% [defined as patients achieving complete response (CR), partial response (PR), or stable disease (SD)]. PR was seen in 33% of cases; progressive disease (PD) was noted in 29%. Post-initial treatment, patients survived for a median 9 months (range, 6.01–14.1 months) after their first radioembolization treatment, and survival from the time of diagnosis of liver metastasis was 21.8 months (range, 14.2–40.2 months). Conclusions: For patients with nonresectable metastasis of cancer to the liver, Y-90 radioembolization is a safe and well-tolerated procedure and a potentially useful option in hepatic malignancies that are not satisfactorily addressed by existing treatment modalities. This data suggest that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center is consistent with preexisting evidence. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic chemotherapy.