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Y90 Treatment Research Paper

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In-111 ibritumomab scintigraphy (planar and SPECT) and FDG PET

In-111 ibritumomab scintigraphy (planar and SPECT) and FDG PET/CT before Y-90 ibritumomab treatment in a patient with mantle cell lymphoma.

Author(s): Jimenez-Bonilla JF, Quirce R, Banzo I, Martinez-Rodriguez I, Sainz-Esteban A, Barragan JE, Lopez-Cordovilla JJ, Carril JM

Affiliation(s): Nuclear Medicine Service, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria, Santander, Spain. jjimenez@humv.es

Publication date & source: 2007-12, Clin Nucl Med. 32(12):952-3.

Publication type: Case Reports

We report the case of a 75-year-old man, in whom Y-90 ibritumomab was requested because of relapse of blastoid variant mantle cell lymphoma diagnosed in 1995. Before Y-90 ibritumomab treatment, FDG PET and In-111 ibritumomab scintigraphy with planar views at 24 hours, 48 hours, and 5 days, including SPECT, were performed. Discordant information between both examinations was observed as, in addition to the lesions detected by In-111 ibritumomab imaging, FDG PET detected lesions that did not take up the ibritumomab. The discrepancy shown by both radiotracers has to be kept in mind before planning treatment with Y-90 ibritumomab, and for the correct evaluation of treatment response.

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Editor’s Note:This article is based on research presented at scientific press conferences at the Society of Interventional Radiology’s (SIR) 35th Annual Scientific Meeting in Tampa, Fla. last month. All abstracts can be viewed at www.sirmeeting.org.

Y-90 Embology Therapy
Extends Life in Inoperable Liver Cancers
An embolotherapy procedure placing yttrium-90 (Y-90) microspheres directly into liver tumors shows promise in prolonging life for many liver cancer patients who are not candidates for surgery, according to research presented last month at SIR’s 35th Annual Scientific Meeting in Tampa, Fla.

“This is encouraging news for liver cancer patients, especially those who also have blockage in the portal vein,” said Riad Salem, MD, MBA, director of interventional oncology at the Robert H. Lurie Comprehensive Cancer Center at Northwestern Memorial Hospital in Chicago. “While patients aren’t cured, their lives are being extended and their quality of life is improving with yttrium-90 microsphere treatment. This unique interventional radiology treatment, which combines the radioactive isotope Y-90 into microspheres that deliver radiation directly to a tumor, is a particularly elegant way to give patients a cancer treatment that doesn’t harm the healthy cells. Patients don’t feel sick or have many of the side effects that happen with standard cancer treatments.”

In the study, 291 patients with hepatocellular carcinoma were treated with intra-arterial Y-90 microspheres as part of a single-center prospective study. Researchers administered 526 (average of 1.8) treatments. Researchers reviewed 1,250 scans to assess response and time to progression, a surrogate marker that may imply but does not prove improved survival. Overall time to progression was 7.9 months, according to Salem. In oncologic standards for this disease, he said this is a promising finding.

Patients with Child-Pugh A disease, with or without portal vein thrombosis, benefited the most from Y-90 treatment, with some patients surviving more than 20 months, according to Salem. Child-Pugh A patients with branch portal vein thrombosis survived nearly 17 months.

Toxicities reported included fatigue (57%), transient pain (23%), nausea/vomiting (20%), and exhibited grade 3 to 4 bilirubin toxicity (5%).

The embolotherapy procedure combining Y-90 into microspheres to deliver radiation directly to a tumor allows a higher local dose of radiation to be used without subjecting surrounding healthy tissue to the radiation. Each microsphere is about as wide as five red blood cells. These tiny beads are injected through a catheter from the groin into the liver artery supplying the tumor and become lodged in it.

“These are early promising results. This information can be used to design future Y-90 trials and to describe Y-90 as a potential treatment option to liver cancer patients,” Salem said.

About 18,500 cases of primary liver cancer are diagnosed each year. Primary liver cancer is twice as common in men as women and occurs most frequently in patients with cirrhosis of the liver.

Many patients with liver cancer have impaired liver function due to underlying cirrhosis and/or the tumors themselves. They are then at increased risk for liver toxicity from any liver cancer treatment. In the United States, approximately 50% to 60% of patients with primary liver cancer die of tumor progression, and 40% to 50% die from advancing cirrhosis and subsequent liver failure.

Although the surgical removal of liver tumors offers the best chance for a cure, more than 75% of primary liver cancer patients are not surgical candidates because their tumors may be too large, too numerous, or have grown into major blood vessels or other vital structures. Historically, chemotherapy drugs and external radiation therapy have been ineffective for curing inoperable liver cancer. Due to these patients’ compromised liver function, physicians must be careful that cancer treatments do not cause additional liver damage and toxicity.

“For these patients, minimally invasive treatments offer them an option that can give them more time,” said Salem.

— Source: SIR Abstract 34: “Yttrium-90 Radioembolization for Hepatocellular Carcinoma: Comprehensive Analysis of Long-Term Outcomes in 291 Patients”

Nanoembolization
New Approach to Treat Pancreatic Cancer
Researchers are investigating a nanoembolization treatment using tiny gold nanoparticles for pancreatic cancer treatment. Reed A. Omary, MD, MS, an interventional radiologist and professor of radiology and biomedical engineering and vice chair of research in the radiology department at Northwestern University in Chicago, reported on early research at SIR’s Annual Scientific Meeting.

“As current treatments for pancreatic cancer offer minimal benefit, entirely new approaches are needed,” Omary said. “We’ve developed a radically different approach that might be able to overcome some of the obstacles that have hampered previous therapies for pancreatic cancer.”

Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and carries the worst prognosis of any cancer even when diagnosed early. This aggressive cancer typically has a six-month survival rate at diagnosis. In 2009, an estimated 42,000-plus individuals, typically over the age of 60, were diagnosed with pancreatic cancer, making it the fourth-leading cause of cancer death in the United States. Because it is often found late and spreads quickly, pancreatic cancer can be hard to treat. Traditional treatment attempts include combinations of chemotherapy, radiation therapy, and/or surgery. However, none of these methods results in consistently effective treatment.

Seeking a different approach to treatment, Northwestern researchers constructed gold nanoparticles with cancer-killing agents attached to them. Measuring only 13 nm in diameter, 8,000 of them strung together would be less than the width of a single human hair. In animal studies, the researchers injected the cancer-killing nanoparticles directly into the tumor.

“Using nanoembolization, we dramatically increased the concentration of the nanoparticles in the tumor by 55 times over traditional methods that use a vein (to deliver the drugs),” Omary said. “That’s a massive improvement and a promising discovery for this dreadful disease.”

Omary said one major reason that current pancreatic cancer treatments do not work is that scar tissue develops around the cancer, blocking drugs from entering the tumor.

“We used a catheter to deliver cancer-killing nanoparticles directly to the tumor,” Omary said. “The catheter is placed into an artery near the groin and navigated through blood vessels to the site of the tumor, all without surgery. Once in the blood vessel that supplies the tumor, the catheter can deliver nanoparticles directly into the tumor. This method may offer a better way to overcome the scar tissue that blocks drugs from attacking the tumor.”

He said such catheter delivery permits more drug to be delivered to the tumor compared with injecting it into a vein. In addition, this therapy may have the potential to reduce some side effects such as vomiting and hair loss often seen with typical chemotherapy.
“Researchers have been using the same toolbox for a long time without any benefit. It’s time for us to apply some high-tech tools to treat pancreatic cancer,” said Omary.

— Source: Abstract 71: “Image-Guided Nanoembolization as a Novel Local Therapy for Pancreatic Cancer: Feasibility in an Animal Model”

RF Ablation
Repeatable Treatment Option for Liver Metastases
Radio-frequency ablation (RFA) offers colon cancer patients with liver metastases a repeatable treatment option that can prolong their lives by years, researchers at SIR’s annual meeting reported.

“Patients who have recurrent colon cancer in their liver after surgery can be treated with radio-frequency ablation and avoid repeated liver surgery,” said Constantinos T. Sofocleous, MD, PhD, FSIR, an interventional radiologist at Memorial Sloan-Kettering Cancer Center in New York City. “RFA kills target cancer tissue with heat while sparing the healthy tissue. This is particularly important for patients who develop new colon cancer in the liver after prior surgery. In general, these patients have a smaller amount of liver tissue; another surgery is usually not possible or very difficult and associated with higher risk.”

Approximately one half of colon cancer patients will develop liver metastases at some point during the course of their disease; most of them are not candidates for surgery.

“In those who undergo surgery, recurrence is a serious problem,” Sofocleous said. “Traditionally, chemotherapy has been the only therapy. Radio-frequency ablation is a treatment that can destroy the tumor locally in the liver and, in combination with systemic and local hepatic arterial chemotherapy, it may extend the life of selected patients.”

The study did not make direct comparisons with other treatments, but the patients’ survival rates after RFA were comparable with those of surgery, according to Sofocleous. The researchers treated 56 patients who had multiple prior treatments with surgery, systemic, and local chemotherapy CT-guided RFA over a six-year period. They reported survival rates of 91% at one year, 66% at two years, and 41% at three years. More importantly, Sofocleous noted, the survival rates are in addition to the patients’ survival rates after prior surgery.

Source: Abstract 107: “Radiofrequency Ablation of Recurrent Colorectal Cancer Hepatic Metastases After Hepatectomy”

Cryotherapy
Promising Future Tool for Multifocal Metastases
Cryotherapy may become the treatment of the future for cancer that has metastasized in soft tissues and bones because these patients often are not candidates for surgery, said researchers at SIR’s annual meeting.

“Improved treatment options are needed for individuals affected by metastases in bone and soft tissues since patients with multifocal metastatic disease are often not candidates for surgery,” said Peter J. Littrup, MD, director of imaging research and image-guided therapy for the Barbara Ann Karmanos Cancer Institute in Detroit. “Percutaneous soft tissue cryotherapy is a well-tolerated treatment option, especially for patients with anesthesia risks, painful lesions, or those seeking local control during chemotherapy. Tumor size and/or location do not preclude thorough treatment or pose greater risk with appropriate precautions.”

In the 97-patient study, researchers used sufficiently deadly temperatures to effectively kill tumor cells, resulting in an average 77% tumor shrinkage in patients after 24 months. “Because of the variable placement of tumors within these soft tissue and bone locations, this study shows the versatility of this treatment option when using proper techniques to safeguard nearby structures,” Littrup said. “Aside from the successful tumor control, what makes this technique even more preferable is the excellent tumor shrinkage since the underlying fibrous or collagenous structures are preserved. The body can then better heal at the ablation site with minimal additional scar tissue formation.”

Conservative estimates indicate that up to 500,000 of these newly diagnosed cancer patients alone will suffer from metastatic disease in bone and soft tissue areas. Cryotherapy is a good option for a large common cancer problem, namely the original cancer tumor site or a few unresponsive tumors sites can cause cancer management problems even after a generally good response to chemotherapy and/or radiation therapy, according to Littrup.

“Metastasized tumors can occur nearly anywhere in the body and frequently cannot receive additional radiation therapy or would be difficult or very morbid to be controlled with surgery,” he said. “Cryotherapy was able to preserve quality of life by providing good local treatment with minimal side effects, especially with advanced stages of cancer where any additional treatment is unlikely to provide a systemic cure.” However, he noted that cryotherapy is not a first-line therapy for tumor treatment.

Historically, cryoablation has been performed on the prostate and liver, but this technique has been recently found effective in other tumors, including the breast, kidney, and lung.

“We simply translated this concept to retroperitoneal, intraperitoneal, superficial, and bone locations in order to generate successful use of cryotherapy in different patient groups,” Littrup said. The major benefits of cryotherapy are its superb visualization of the ice treatment zone during the procedure, its low pain profile in an outpatient setting, and its excellent healing with minimal scarring, he said. In this study’s cryotherapy treatment, researchers used several needlelike cryoprobes that were inserted through the skin to deliver extremely cold gas directly to a tumor to freeze it. The “ice ball” that is created around the needle grows in size and destroys the frozen tumor cells. Surgeons and radiation oncologists have long tried to provide at least a 1-cm margin of treatment with cancer tumors, and it was important to assure a similar margin of lethal temperatures beyond all tumor margins by cryotherapy in this study, according to Littrup.

“One of our first soft tissue cryotherapy patients with recurrent ovarian cancer encouraged us to really begin this study,” he explained. “She appropriately noted that with recurrent cancer, second- and third-line chemotherapy drugs can run up to $20,000 to $60,000 per month and that additional debulking surgery needed at least an additional month of recovery.”

The patient had undergone seven cryoablation procedures over the previous five years in combination with only a few additional cycles of chemotherapy when more than two recurrences were noted, according to Littrup, noting that she deemed cryotherapy a ”holiday” from chemotherapy and has become an advocate for the procedure.

In the study, 157 CT- or ultrasound-guided percutaneous cryotherapy procedures were performed (retroperitoneal, 30; intraperitoneal, 51; superficial, 47; and bone, 29) in 97 patients. Doctors used thermocouple monitoring, saline injection, and/or direct skin warming to protect healthy tissue from being frozen. Patients subsequently underwent CT or MRI. The cryotherapy zone was well defined as a hypodense ice ball with an average ablation diameter of 5.4 cm with an average tumor diameter of 3.5 cm.

Littrup noted that further study is needed to determine the optimum probe number, spacing, and freeze times needed to produce thorough ice coverage of all soft tissue tumors.

— Source: Abstract 155: “Soft Tissue Cryotherapy: Initial Experience and Intermediate Follow-Up in Retroperitoneal, Intraperitoneal, Superficial and Bone Locations”

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for unresectable primary and metastatic liver tumors

Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for unresectable primary and metastatic liver tumors Background

The aim of this study was to evaluate the success of selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) microspheres in liver metastases of different tumors. We also interpreted the contribution of SIRT to survival times according to responder- non responder and hepatic- extra hepatic disease.

The clinical and follow-up data of 124 patients who were referred to our department for SIRT between June 2006 and October 2010 were evaluated retrospectively. SIRT has been applied to 78 patients who were suitable for treatment. All the patients had primary liver tumor or unresectable liver metastasis of different malignancies. The treatment was repeated at least one more time in 5 patients to the same or other lobes. Metabolic treatment response evaluated by fluorine-18 fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) in the 6 th week after treatment. F18-FDG PET/CT was repeated in per six weeks periods. The response criterion had been described as at least 20% decrease of SUV value. Also in patients with neuroendocrine tumor serial Gallium-68 (Ga-68) PET/CT was used for evaluation of response. Patients were divided into 2 groups according to their treatment response.

68 patients received treatment for the right lobe, seven patients received treatment for the left lobe and 3 patients for both lobes. The mean treatment dose was estimated at 1.62 GBq. In the evaluation of treatment response; 43(55%) patients were responder (R) and 35 (45%) patients were non-responder (NR) in the sixth week F18-FDG PET/CT. Mean pretreatment SUVmax value of R group was 11.6 and NR group was 10.7. While only 11 (31%) out of 35 NR patients had H disease, 30 (69%) out of 43 R patients had H disease (p < 0.05). The mean overall survival time of R group was calculated as 25.63 ± 1.52 months and NR group's 20.45 ± 2.11 (p = 0.04). The mean overall survival time of H group was computed as 25.66 ± 1.52 months and EH group's 20.76 ± 1.97 (p = 0.09).

Conclusions

SIRT is a useful treatment method which can contribute to the lengthening of survival times in patients with primary or metastatic unresectable liver malignancies. Also F18-FDG PET/CT is seen to be a successful imaging method in evaluating treatment response for predicting survival times in this patient group.

Selective intraarterial radionuclide therapy (SIRT) liver tumors survival times

Background

Primary or metastatic tumors of the liver generally have poor prognosis and are responsible for the shortening of overall survival times. Radioembolization with Yttrium-90 (Y-90) labeled microspheres (SIR spheres) (SIRT) is a palliative treatment method which could be applied to patients with unresectable liver tumors [ 1 – 3 ]. SIRT, firstly had been developed for the use of the treatment of unresectable hepatocellular carcinoma patients. Since then it has been used for the treatment of liver metastasis of different cancers [ 4 – 7 ]. Radiopharmaceutical includes resin bases microspheres which are labeled as Y-90. The diameter of spheres is approximately 29-35 μm. Although the portal venous system supplies the majority of the blood flow of normal liver tissue, liver metastases obtain almost all their blood flow by the hepatic artery. This situation is the principle of SIRT. Y-90 labeled microspheres which are applied to the hepatic artery cause micro embolization in the hepatic arterioles. In addition, Y-90 has beta particles, 64 hours' half-life and a 2.4 mm tissue penetration. In this way, in addition to mechanical obstruction, 30-60 Gray radiation doses are delivered to tumor tissue associated with applied Y-90 doses [ 8 ]. As a result, the surrounding liver tissue is protected.

The aim of this study was to evaluate the success of SIRT with Y-90 microspheres in liver metastases of different tumors. We also interpreted the contribution of SIRT to survival times according to responder- non responder and hepatic- extra hepatic disease.

Patients and method

The clinical and follow-up data of 124 patients who were referred to our department for SIRT between June 2006 and October 2010 were evaluated retrospectively. SIRT has been applied to 78 patients who were suitable for treatment. Of the remaining 46 out of 124 patients, the treatment could not have been performed because of the main contraindications of SIRT such as bilirubin levels>2 mg/dl or 5 fold elevation of AST and ALT levels or albumin levels< 3 mg/dl or bulky tumor>70% of liver tissue. All the patients had unresectable liver metastasis of different malignancies (35/78 colorectal, 25/78 hepatocellular, 7/78 gastric, 4/78 breast, 1/78 malign melanoma, 1/78 pancreas, 1/78 renal cell, 1/78 esophagus and 3/78 neuroendocrine tumor patients). All the patients had received chemotherapy for the treatment of primary tumors. Furthermore, all of them had taken chemotherapy for liver metastases and they had been accepted as refractory to chemotherapy. Partial hepatectomy, chemoembolization and radiofrequency ablation treatment had been performed in 2, 2 and 6 patients respectively. The treatment was repeated at least one more time in 5 patients to the same or other lobes.

All the patients underwent liver function tests and dynamic liner MRI as well as basal F18-FDG PET/CT examination before the treatment. The first control F18-FDG PET/CT scan was undergone by all patients 6 weeks after treatment for the evaluation of treatment response.

The patients were divided into two groups according to the disease stage; those with only liver metastases (H) and those with metastases in other organs (EH).

Selective intraarterial radionuclide therapy (SIRT)

In all patients, widely accepted parameters regarding liver reserve, bone marrow reserve (granulocytes > 1500/μL, platelets > 60000/μL), and hepatic vascularity were used as inclusion and exclusion criteria. Liver reserve was evaluated using bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels in blood. A bilirubin level < 2 mg/dl and AST/ALT/ALP levels less than 5 times the normal upper limit were required for radioembolization. 10 patients did not receive the therapy according to these criteria. Patients with ascites, portal hypertension, portal venous thrombosis or an expected survival < 3 months were excluded as well as the patients with contraindications for angiography and selective visceral catheterization. To evaluate vascular tree, a therapy-planning angiogram was performed. With this angiogram, branches of hepatic artery to the gastrointestinal tract were coiled to prevent Y-90 reflux to the stomach, i.e. to gastro-duodenal artery and right gastric artery. At the end of this planning angiogram, a 150 MBq dose of 99m Tc-labelled macroaggregated albumin (MAA) was administered through the catheter in an attempt to detect arteriovenous shunts from the hepatic arterial system to the pulmonary system or gastrointestinal tract. After this procedure, gamma imaging was obtained and regions of interest were drawn around the liver and lungs in anterior planar images, and the pulmonary shunt was calculated using the following equation: pulmonary shunt fraction = ROI lung counts /(ROI lung counts + ROI liver counts. Patients with a pulmonary shunt less than 20% were eligible for therapy. 2 patients were excluded because of the pulmonary shunt higher than 20%. In 78 patients who were suitable for therapy, the Y-90 dose was adjusted according to the following body surface area method: activity (GBq) = (BSA - 0.2) + tumor volume/total liver volume. The Y-90 resin microspheres (Sirtex Medical, Australia) were injected through the hepatic artery catheter under intermittent fluoroscopic visualization. Within 1 to 24 hours after microsphere infusion, Bremsstrahlung images were obtained to confirm that the Y-90 was deposited only in the liver. All patients were hospitalized overnight and medications like analgesics, antiemetic, and H2 antagonist were administered, if necessary. All patients were closely monitored until acute or late toxicities were resolved.

PET/CT imaging

PET/CT images were acquired with GE Discovery ST PET/CT scanner. During imaging patients were required to have at least 6 hours fasting and checked if their blood glucose levels were under 150 mg/dl. Oral contrast agents were applied to all patients. Images were obtained while patients were lying in a supine position from vertex to proximal femur. Whole body F18-FDG PET/CT imaging was performed approximately 1 hour after an intravenous injection of 8-10 mCi FDG. During the waiting period patients rested in a quiet room without receiving muscle relaxant. PET images were acquired for 4 minutes per bed position. Emission PET images were reconstructed with non-contrast CT. A CT image was obtained from the patient's integrated F18-FDG PET/CT with the use of a standardized protocol involving 140 kV, 70 mA, a tube rotation time of 0.5 s per rotation, a pitch of 6 and a section thickness of 5 mm. Patients were allowed to breathe normally during procedure. Attenuation-correction was done by PET/CT fusion images on three planes (trans-axial, coronal and sagittal) and were reviewed on Xeleris Workstation (GE Medical System). F18-FDG PET/CT images were evaluated visually and semi-quantitatively by two experienced nuclear medicine specialists. The number, location and SUV values of liver lesions were recorded.

Evaluation of treatment response

Metabolic treatment response evaluated by PET/CT in the 6 th week after treatment. FDG-PET/CT was repeated in per six weeks periods. The response criterion had been described as at least 20% decrease of SUV value. Also in patients with neuroendocrine tumor serial Ga-68 PET/CT was used for evaluation of response. Patients were divided into 2 groups according to their treatment response (R = responder, NR = non-responder).

Statistical analysis

According to R, NR, H and EH groups, overall survival analysis was performed using Kaplan-Meier method and comparison was done using the log rank (Mantel-Cox) test. SPSS version 15.0 was used for statistical analysis. Statistical significance was as accepted p < 0.05.

78 patients (49 M; 29 F; mean age: 62.4 ± 2.3 years) received intraarterial radionuclide therapy with Y-90 microspheres for liver metastasis or primary HCC between June 2006 and October 2010. Although 25 patients had primary HCC diagnosis, the remainder had unresectable multiple liver metastases of different cancers (35 colorectal, 7 gastric, 4 breast, 1 pancreas, 1 renal cell, 1 esophagus cancer, 3 neuroendocrine tumor and 1 malignant melanoma).

Radiation Delivery

68 patients received treatment for the right lobe, seven patients received treatment for the left lobe and 3 patients for both lobes. The mean treatment dose was estimated at 1.62 GBq (range: 1-1.8 GBq). In all patients, the leakage to the lungs was less than 20%. Therefore, neither reduction in the estimated dose nor discontinuation of the treatment was required.

The technical success of the intraarterial delivery of Y-90 microspheres was 100% and none of the patients experienced complications due to angiographic intervention. All patients experienced post-radioembolization syndrome characterized by mild abdominal pain, nausea, and sub-febrile fever. A combination of a non-opioid analgesic, an antiemetic and a H2 receptor blocker was given to patients not tolerating these symptoms. Symptoms decreased in intensity within one week and completely disappeared within 15 days. No difference has been found in complication rates between the two lobes. Bremsstrahlung imaging done 24 hours after treatment did not show any activity outside the liver. All patients were hospitalized for one night as a preventive measure and prolonged hospitalization was not required by any of the patients.

In the evaluation of treatment response; 43 (55%) patients were responder (R) (Figure 1. 2. 3 ) and 35 (45%) patients were non-responder (NR) in the sixth week F18-FDG PET/CT. Mean pretreatment SUVmax value of R group was 11.6 and NR group was 10.7. While only 11 (31%) out of 35 NR patients had H disease, 30 (69%) out of 43 R patients had H disease (p < 0.05) (Table 1 ).

Cumulative survival curves of the R, NR, H and EH subgroups in the whole patient group. Time: months, R: responder, NR: nonresponder, H: hepatic, EH: extrahepatic.

Cumulative survival curves of the R, NR, H and EH subgroups in the colorectal group. Time: months, R: responder, NR: nonresponder, H: hepatic, EH: extrahepatic.

Cumulative survival curves of the R, NR, H and EH subgroups in the HCC group. Survival: months, R: responder, NR: nonresponder, H: hepatic, EH: extrahepatic.

H and EH disease rates of the R and NR groups.

Survival analysis

The mean overall survival time of R group was calculated as 25.63 ± 1.52 months and NR group's 20.45 ± 2.11 (p = 0.04) (Table 2. 3 ). The mean overall survival time of H group was computed as 25.66 ± 1.52 months and EH group's 20.76 ± 1.97 (p = 0.09) (Table 4. 5 ). The survival curves of the whole patient group, the colorectal group and the HCC group, according to the treatment response and disease stage were demonstrated in Figure 4. 5 and 6. respectively.

The mean and median survival times of the R and NR groups.

Means and Medians for Survival Time

95% Confidence Interval

95% Confidence Interval

a. Estimation is limited to the largest survival time if it is censored.

Mantel-cox overall comparison of the R and NR groups.

Log Rank (Mantel-Cox)

Test of equality of survival distributions for the different levels of response.

The mean and median survival times of the H and EH groups.

60 years-old male patient who took 1.2GBq Y-90 microsphere therapy to the right lobe of the liver for HCC. 4A, 4B: axial- fused and PET images of the liver before the treatment. 4C, 4D: axial- fused and PET images of the liver after the treatment.

39 years-old male patient who received 1.6 GBq Y-90 microsphere therapy to the right and left lobe in separate sessions for primary hemangioendothelioma of the liver. 5A; coronal CT, 18F-FDG PET, fused and maximum intensity projection images of the whole body before the treatment. 5B; coronal CT, 18F-FDG PET, fused and maximum intensity projection images of the whole body after the treatment.

54 years-old male patient who received 1.7 GBq Y-90 microsphere therapy to the right and left lobes in separate sessions for liver metastases of colorectal cancer. 6A; coronal CT, 18F-FDG PET, fused and maximum intensity projection images of the whole body before the treatment. 6B; coronal CT, 18F-FDG PET, fused and maximum intensity projection images of the whole body after the treatment of the right lobe. 6C; coronal CT, 18F-FDG PET, fused and maximum intensity projection images of the whole body after the treatment of the left lobe.

Discussion

As mainly HCC, colorectal cancer and neuroendocrine tumors; SIRT has been used for the treatment of liver metastasis of several tumors and primary hepatocellular cancer. There have been different results in literature about the success of SIRT in liver metastasis of different tumors. It has been reported that the efficiency of SIRT in liver metastases of colorectal cancer was 90% in first-line therapy and 80% in second-line therapy [ 9 ]. In our patient group, we detected a rate of response as 55%. This rate might appear low, but from a recent study, we accepted a different response criterion as a 20% decrease in SUV levels of liver lesions. Our patient group also included 78 patients with different malignancies. The biological behavior of liver metastases of different tumor might vary. Furthermore all the patients received SIRT as a salvage therapy. Our response rate might have been affected for these reasons.

We preferred F18-FDG PET/CT for staging before the treatment and evaluation of treatment response. There are many advantages of F18-FDG PET/CT in the early stage after therapy. Firstly, it is known that F18-FDG PET/CT is more successful than conventional imaging methods in evaluating treatment response at the early period after SIRT [ 8. 10 ]. Also Wong et al. have reported that there is a correlation between liver tumor burden and the presence of extra-hepatic disease detected by PET/CT before Y-90 microspheres treatment [ 11 ]. So, F18-FDG PET/CT may provide extra information in predicting the development of extra-hepatic disease.

In different studies, the survival times after Y-90 microsphere treatment of liver metastases had been reported between 6.7 and 17.0 months [ 12 – 20 ]. These periods may change according to the microsphere type used, previous chemotherapy regimens and patient groups. For this reason, it would be an optimal approach to make a comparison with an age, diagnosis, stage and chemotherapy matched control group. Since in our study, the treatment was applied as a salvage protocol to most of the patients, it is very difficult to find a control group which has patients with same diagnosis and same stage of disease. For this reason we compared the survival times of our groups to current literature. It has been calculated that mean survival times of R and NR groups as 25.63 ± 1.52 and 20.45 ± 2.11 months (p = 0.04) respectively. Because the difference between the two groups was statistically significant, SIRT is seem to be beneficial in the treatment of liver tumors. However this study is a retrospectively designed study which has small heterogeneous patient number, new prospective randomized studies are needed to support this result. Also results of this study support the conclusion which is that FDG PET/CT is a useful method for evaluating treatment response in patients who have undergone SIRT for liver metastasis. In the subgroup analysis; mean overall survival time of colorectal patients group was found to be 20.5 months while the R and NR groups' were 21.35 and 18.28 months respectively. In the HCC group; the mean overall survival, R and NR groups' survival times were 25.8, 18.24 and 29.5 months respectively.

The treatment response was also evaluated according to the disease stage with H and EH groups. The mean overall survival time of the H group was computed as 25.66 ± 1.52 months and EH group's 20.76 ± 1.97 (p = 0.09). The difference between the two groups was not statistically significant but it was very close to the limit of p = 0.05. In the subgroup analysis of colorectal patients group, the mean survival time of H and EH groups were 23.12 and 17.08 months respectively. In the HCC group; the H and EH groups' survivals were 27.2 and 23.9 months respectively. In the separate evaluation of patients according to diagnosis, the difference between the R and NR groups and E and EH groups was not statistically significant. This result could be related to the fact that the numbers of each patient group were small in the separated analysis. For this reason, larger prospective randomized new studies are needed.

Conclusion

SIRT is a useful treatment method which can contribute to the lengthening of survival times in patients with primary or metastatic unresectable liver malignancies. Also F18-FDG PET/CT is seen to be a successful imaging method in evaluating treatment response for predicting survival times in this patient group.

Department of Radiology, Faculty of Medicine, Ankara University

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