yttrium-90 ( y ) microsphere radioembolization is an emerging treatment for metastatic hepatic malignancies . in this procedure , 2060 micron - sized -radiation - emitting particles are administered to liver tumors using a transcatheter approach to deliver high - dose localized internal radiation .
this therapy takes advantage of the predominant hepatic arterial flow to liver tumors ; cancerous tissue derives 80100% of its blood supply from the hepatic arterial system , while normal liver gains 7580% of its perfusion from the portal vein .
radioactive microspheres delivered from a catheter in the hepatic artery are preferentially deposited in malignant tissue at a 3:1 to 20:1 ratio compared to normal liver , and result in high tumor response rates and extended survival .
while the use of y radioembolization for treatment of hepatic metastases from colorectal , neuroendocrine , and breast cancer   has been broadly investigated , application of this therapy toward management of lung cancer hepatic metastases has not been extensively documented .
herein , we present 2 cases of effective y radioembolization for treatment of chemorefractory lung cancer hepatic metastases , and highlight the potential coadjuvant value of this procedure in patients with stage 4 lung cancer and liver - dominant metastatic disease .
institutional review board approval is not required for small retrospective case studies at the authors hospital . a 68-year - old woman with a 50-pack - year smoking history presented with a complaint of dyspnea and cough .
she underwent a chest radiograph followed by computed tomography ( ct ) , which revealed a 4.8  2.8 cm mass in the upper lobe of the left lung ( fig .
a bronchoscopy was performed 3 months after presentation for tissue diagnosis , but both bronchoalveolar lavage and transbronchial needle aspirate were negative for malignancy .
the patient was then referred to interventional radiology ( ir ) for ct - guided transthoracic biopsy , which yielded a diagnosis of well - differentiated squamous cell carcinoma .
work - up with whole - body positron emission tomography ( pet ) and brain magnetic resonance imaging demonstrated stage 3b ( t4n2m0 ) disease .
as such , the patient was not a candidate for surgical resection , and was placed on chemoradiation treatment .
she was given cisplatin and etoposide for 1 cycle , and was treated with a 66-gy radiation dose using 2-field 3-dimensional conformal radiotherapy .
the patient was subsequently followed with ct imaging ; a scan performed 2 months after therapy showed size reduction of the primary tumor to 4.6  2.2 cm , but also demonstrated a new 2.0  1.9 cm lesion in the right hepatic lobe suspicious for metastasis .
she was started on second - line chemotherapy 2 months later with carboplatin auc6 and paclitaxel .
follow - up ct 4 months later showed smaller size of the lung mass ( fig .
1a ) , but increased size of the hepatic metastasis to 4.3  4.3 cm ( fig .
the patient was therefore started on third - line chemotherapy with gemcitabine for 4 cycles .
ct scan 2 months after completing chemotherapy showed no decrease in the size of the hepatic metastasis and revealed a new 0.9 cm satellite lesion . at this point ,
the patient was referred to ir for transcatheter treatment of her lung cancer hepatic metastases .
given good baseline performance status , with eastern cooperative oncology group ( ecog ) status 1 , as well as preserved liver function , the patient was a good candidate for y microsphere therapy . in preparation for treatment ,
m macroaggregated albumin ( tc - maa ) scan for lung shunt fraction ( lsf ) calculation .
1c ) , and the hepatic vascular anatomy was found to be amenable for y therapy .
5.4 mci of tc - maa was administered from the right hepatic artery for lsf analysis .
finally , the femoral vascular access was removed and hemostasis was accomplished by manual compression .
tc - maa scan demonstrated a hepatopulmonary shunt fraction of 17.7% , below the 20% threshold for safe treatment .
the radioembolization procedure was scheduled for 1 week later . on the day of the treatment procedure ,
an approximately 120-gy radiation dose was administered via injection of 3 gbq of y - labeled glass microspheres ( therasphere ; mds nordion , ottawa , ont . , canada ) .
completion angiography was performed , all vascular devices were removed , and access site hemostasis was achieved by manual compression . after an uneventful post - procedure recovery , the patient was seen 1 month later .
ct scan at that time demonstrated complete necrosis of the right hepatic lesion ( fig .
1d ) , and pet ct scan performed 2 months after treatment showed no evidence for residual viable tumor ( fig .
at present , the patient is alive with persistent complete response in the treated liver lesion 28 months after initial diagnosis , 21 months after progression to stage 4 disease , and 11 months after y therapy . of note , she has since undergone 2 additional successful hepatic radioembolization procedures to treat new small metastases that developed since the time of initial liver therapy . a 53-year - old woman with a history of stage 1b ( t2n0m0 ) left lung squamous cell carcinoma status post lobectomy and adjuvant chemotherapy with carboplatin and paclitaxel 2 years prior presented for evaluation of a solid mass on the left tongue undersurface .
biopsy demonstrated poorly differentiated squamous cell carcinoma , and the patient underwent wide local excision of the floor of mouth and left tongue , bilateral neck dissection , and flap reconstruction .
one month after surgery , the patient was placed on cisplatin chemoradiation therapy during which time she received a total dose of 66 gy . upon completion of adjuvant therapy
, she subsequently underwent pet ct imaging surveillance , and 11 months later was found to have a new 2.8  2.4 cm left hepatic lobe mass .
ultrasound - guided biopsy was positive for metastatic squamous cell carcinoma consistent with the patient 's lung primary tumor .
the patient was placed on a second round of chemotherapy using cisplatin , 5-fluorouracil , and cetuximab .
she was also referred to ir for concomitant transcatheter treatment of her lung cancer hepatic metastasis ; given good performance status ( ecog 0 ) and preserved liver function , y radioembolization was selected .
the patient underwent mapping arteriogram in preparation for y radioembolization , performed from a conventional femoral artery approach . left hepatic artery arteriogram demonstrated a hypervascular left hepatic lobe tumor ( fig .
2b ) , and the hepatic vascular anatomy was found to be amenable for y radioembolization therapy .
5.4 mci of tc - maa was then administered from the proper hepatic artery for lsf analysis .
finally , the femoral vascular access was removed and hemostasis was accomplished by manual compression .
the radioembolization procedure was scheduled for 1 month later . on the day of the treatment procedure ,
an approximately 120-gy radiation dose was administered via injection of 1.57 gbq of y - labeled glass microspheres ( therasphere ; mds nordion ) .
completion angiography was performed , all vascular devices were removed , and access site hemostasis was achieved by manual compression . following y administration , correct tumor targeting
the patient experienced an uneventful post - procedure recovery and is currently continuing with her 6-cycle chemotherapy regimen .
pet ct performed 2 months after y treatment showed complete tumor response without evidence for residual tumor ( fig .
at present , the patient is alive without active disease 16 months after initial diagnosis , 4 months after progression to stage 4 disease , and 2 months after y radioembolization therapy .
a 68-year - old woman with a 50-pack - year smoking history presented with a complaint of dyspnea and cough .
she underwent a chest radiograph followed by computed tomography ( ct ) , which revealed a 4.8  2.8 cm mass in the upper lobe of the left lung ( fig .
a bronchoscopy was performed 3 months after presentation for tissue diagnosis , but both bronchoalveolar lavage and transbronchial needle aspirate were negative for malignancy .
the patient was then referred to interventional radiology ( ir ) for ct - guided transthoracic biopsy , which yielded a diagnosis of well - differentiated squamous cell carcinoma .
work - up with whole - body positron emission tomography ( pet ) and brain magnetic resonance imaging demonstrated stage 3b ( t4n2m0 ) disease .
as such , the patient was not a candidate for surgical resection , and was placed on chemoradiation treatment .
she was given cisplatin and etoposide for 1 cycle , and was treated with a 66-gy radiation dose using 2-field 3-dimensional conformal radiotherapy .
the patient was subsequently followed with ct imaging ; a scan performed 2 months after therapy showed size reduction of the primary tumor to 4.6  2.2 cm , but also demonstrated a new 2.0  1.9 cm lesion in the right hepatic lobe suspicious for metastasis .
she was started on second - line chemotherapy 2 months later with carboplatin auc6 and paclitaxel .
follow - up ct 4 months later showed smaller size of the lung mass ( fig .
1a ) , but increased size of the hepatic metastasis to 4.3  4.3 cm ( fig .
the patient was therefore started on third - line chemotherapy with gemcitabine for 4 cycles .
ct scan 2 months after completing chemotherapy showed no decrease in the size of the hepatic metastasis and revealed a new 0.9 cm satellite lesion . at this point ,
the patient was referred to ir for transcatheter treatment of her lung cancer hepatic metastases . given good baseline performance status , with eastern cooperative oncology group ( ecog ) status 1 , as well as preserved liver function ,
the patient was a good candidate for y microsphere therapy . in preparation for treatment ,
m macroaggregated albumin ( tc - maa ) scan for lung shunt fraction ( lsf ) calculation .
1c ) , and the hepatic vascular anatomy was found to be amenable for y therapy .
5.4 mci of tc - maa was administered from the right hepatic artery for lsf analysis .
finally , the femoral vascular access was removed and hemostasis was accomplished by manual compression .
tc - maa scan demonstrated a hepatopulmonary shunt fraction of 17.7% , below the 20% threshold for safe treatment .
on the day of the treatment procedure , a 5-french catheter and coaxial 3-french microcatheter were advanced into the right hepatic artery .
an approximately 120-gy radiation dose was administered via injection of 3 gbq of y - labeled glass microspheres ( therasphere ; mds nordion , ottawa , ont . ,
completion angiography was performed , all vascular devices were removed , and access site hemostasis was achieved by manual compression . after an uneventful post - procedure recovery , the patient was seen 1 month later .
ct scan at that time demonstrated complete necrosis of the right hepatic lesion ( fig .
1d ) , and pet ct scan performed 2 months after treatment showed no evidence for residual viable tumor ( fig
at present , the patient is alive with persistent complete response in the treated liver lesion 28 months after initial diagnosis , 21 months after progression to stage 4 disease , and 11 months after y therapy . of note , she has since undergone 2 additional successful hepatic radioembolization procedures to treat new small metastases that developed since the time of initial liver therapy .
a 53-year - old woman with a history of stage 1b ( t2n0m0 ) left lung squamous cell carcinoma status post lobectomy and adjuvant chemotherapy with carboplatin and paclitaxel 2 years prior presented for evaluation of a solid mass on the left tongue undersurface .
biopsy demonstrated poorly differentiated squamous cell carcinoma , and the patient underwent wide local excision of the floor of mouth and left tongue , bilateral neck dissection , and flap reconstruction .
one month after surgery , the patient was placed on cisplatin chemoradiation therapy during which time she received a total dose of 66 gy . upon completion of adjuvant therapy
, she subsequently underwent pet ct imaging surveillance , and 11 months later was found to have a new 2.8  2.4 cm left hepatic lobe mass .
ultrasound - guided biopsy was positive for metastatic squamous cell carcinoma consistent with the patient 's lung primary tumor .
the patient was placed on a second round of chemotherapy using cisplatin , 5-fluorouracil , and cetuximab .
she was also referred to ir for concomitant transcatheter treatment of her lung cancer hepatic metastasis ; given good performance status ( ecog 0 ) and preserved liver function , y radioembolization was selected .
the patient underwent mapping arteriogram in preparation for y radioembolization , performed from a conventional femoral artery approach . left hepatic artery arteriogram demonstrated a hypervascular left hepatic lobe tumor ( fig .
2b ) , and the hepatic vascular anatomy was found to be amenable for y radioembolization therapy .
5.4 mci of tc - maa was then administered from the proper hepatic artery for lsf analysis .
finally , the femoral vascular access was removed and hemostasis was accomplished by manual compression .
the radioembolization procedure was scheduled for 1 month later . on the day of the treatment procedure
, a 5-french catheter and coaxial 3-french microcatheter were advanced into the left hepatic artery .
an approximately 120-gy radiation dose was administered via injection of 1.57 gbq of y - labeled glass microspheres ( therasphere ; mds nordion ) .
completion angiography was performed , all vascular devices were removed , and access site hemostasis was achieved by manual compression . following y administration , correct tumor targeting was confirmed by bremsstrahlung imaging ( fig .
the patient experienced an uneventful post - procedure recovery and is currently continuing with her 6-cycle chemotherapy regimen .
pet ct performed 2 months after y treatment showed complete tumor response without evidence for residual tumor ( fig .
at present , the patient is alive without active disease 16 months after initial diagnosis , 4 months after progression to stage 4 disease , and 2 months after y radioembolization therapy .
lung cancer is the most common malignancy worldwide and a significant cause of global morbidity and mortality .
an estimated 1,600,000 new cases and 1,380,000 deaths occurred internationally in 2008 , and a projected 226,000 new cases and 160,000 deaths are expected in the united states in 2012 .
liver metastases complicate approximately 6% of lung cancer cases at the time of initial diagnosis , and hepatic tumor spread occurs in up to 36% of patients over the course of their disease .
10% 5-year survival rates , and is most commonly treated with palliative systemic chemotherapy . new treatment approaches for this challenging disease stage are necessary to improve discouraging survival outcomes , and a role for targeted transcatheter therapy in the treatment of lung cancer liver metastases has been recently suggested in small clinical studies [ 9 , 16 ] .
radioembolization is a minimally invasive targeted therapy that selectively delivers internal -radiation via the arteries that supply tumors .
radioembolization describes the mode of action of this procedure , in that embolic particles act as a vehicle for delivery and administration of radiation .
y is a pure -emitting isotope with a half - life of 64.2 h , after which it decays into stable zirconium .
the average energy of -emission is 0.9367 mev , and the mean tissue penetration is 2.5 mm .
one gbq ( 27 mci ) of y provides a 50-gy dose to 1 kg of liver tissue ; 120-gy tumoricidal doses are typically administered during treatment procedures .
glass ( therasphere ; mds nordion ) and resin ( sir - sphere ; sirtex medical , lane cove , n.s.w .
because y radioembolization targets tumors through a transarterial route , a planning angiographic study is required to assess visceral anatomy , identify anatomic variants , isolate the hepatic circulation , and determine tumor location for appropriate catheter placement .
both the planning and treatment procedures may be performed on an outpatient basis . in the present case series , we effectively devitalized 2 large lung cancer metastatic nodules using y radioembolization . in both cases ,
the liver nodules represented the dominant site of active disease and were refractory to systemic chemotherapy , showing enlargement or viability despite standard of care pharmacologic treatment .
both patients showed no pet active disease in the index lesion at 10 and 2 months after treatment , indicating robust and durable complete response to therapy and significant tumor cytoreduction using the targeted treatment approach .
while patients in each case were administered a treatment dose of 120 gy , tumor hypervascularity and preferential blood flow dictates that each lesion likely received a several thousand gy dose , far exceeding 120-gy tumoricidal levels , while normal liver parenchyma contracted low doses approximating 1020 gy , minimizing risk for radiation hepatitis . in this manner ,
internal y radiotherapy allows for higher cytotoxic radiation doses than traditional external beam therapy by making use of internal targeted delivery . to date , the application of y radioembolization therapy toward treatment of lung cancer hepatic metastases has been specifically described in one small clinical series . in 2008 , murthy et al .   reported on 6 patients with liver - dominant lung cancer spread who underwent y treatment .
disease control was achieved in 3 of 6 ( 50% ) patients , while 3 of 6 ( 50% ) patients developed progressive disease .
these suboptimal outcomes may be explained on the basis of advanced disease among treated patients , of which two - thirds had multifocal bilobar liver metastases at the time of y therapy .
in contrast , our patients were treated earlier in the disease course in the setting of solitary liver metastases that could be specifically targeted with an extraordinarily high radiation dose .
our encouraging outcomes suggest need for further investigations to assess the role of early y radioembolization in combination with systemic chemotherapy for lung cancer liver metastases ; this treatment approach has precedent in similar ongoing trials for cancers such as metastatic colorectal carcinoma .
the effect of non - target pulmonary radiation is an important consideration in patients with lung cancer liver metastases who undergo y radioembolization , particularly those with a history of lobectomy or prior radiation , in order to avoid untoward effects on pulmonary function .
current standard of care with y treatment requires performance of a tc - maa scan in order to calculate a lsf prior to radioembolization ; non - target pulmonary deposition of microspheres may occur due to systemic passage of particles via small intrahepatic peri - tumoral arteriovenous communications .
while the incidence of radiation pneumonitis is well below 1% if standard dosimetry models are used [ 20 , 21 ] , single - session doses do not exceed 30 gy , and total doses do not surpass 50 gy , high lsfs resulting in greater lung doses may necessitate y dose reduction to avoid radiation pneumonitis .
for comparison , patients receiving external beam radiation treatment for lung cancer are usually given approximately 60-gy doses , but the lung volume irradiated with > 20 gy is minimized to decrease risk of pneumonitis . in summary , we describe 2 cases of lung cancer liver metastases successfully treated with y radioembolization . in both cases ,
tumors were effectively devitalized and both patients showed excellent clinical outcome . while our clinical observations are made on the basis of a small sample size and should not be overstated , the promising results herein affirm the utility of y radioembolization for targeted treatment of liver metastases , and underscore the need for future investigation into such treatment strategies for advanced lung cancer .
 because stage 4 lung cancer is associated with dismal 5-year survival rates , new treatment approaches targeting extrapulmonary disease are necessary . 
 yttrium-90 microsphere radioembolization is an emerging treatment for metastatic hepatic malignancies that results in high tumor response rates and extended patient survival . to date , 
 application of this therapy toward management of lung cancer hepatic metastases has not been extensively described . 
 herein , we present 2 cases of effective yttrium-90 radioembolization for treatment of lung cancer hepatic metastases , and emphasize the potential coadjuvant value of this procedure in patients with advanced - stage lung cancer and liver - dominant metastatic disease . 
Introduction
Case Reports
Case 1
Case 2
Discussion
Disclosure Statement