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TARE Treatment - Transarterial Radioembolization
Interventional Radiology

TARE Treatment - Transarterial Radioembolization

About This Department

 
Interventional Radiology and Nuclear Medicine

Millions of radioactive beads, each a third the width of a hair, carried by the blood into a liver tumor. The dose is planned to the gray, and the dose decides the result.

Transarterial radioembolization delivers radiation to liver tumors from inside their own blood supply. A catheter travels from the wrist or groin into the hepatic artery, and glass or resin microspheres loaded with yttrium-90 lodge in the small vessels of the tumor, where they irradiate it from within for about two weeks. In the LEGACY study of 162 patients with a single unresectable liver cancer, 88 percent of tumors responded and 87 percent of patients were alive three years later. In a randomized trial, planning the dose to the tumor instead of the liver lobe doubled the response rate, from 36 to 71 percent.

88 in 100
Solitary liver cancers responding, Hepatology 2021
71% vs 36%
Response with personalized against standard dosing, Lancet Gastroenterol Hepatol 2021
27.7% vs 50.6%
Severe side effects, radioembolization against sorafenib, J Clin Oncol 2018
Free
Review of your liver scans and function tests
Free consultation
Send the latest CT or MRI of the liver with the report, liver function tests including bilirubin and albumin, the pathology or the diagnosis as it stands, any chemotherapy given so far, and previous liver treatments. An interventional radiologist and a hepatologist tell you whether radioembolization fits your case, whether a single tumor could be treated with a curative dose, and how the two visits it requires would be planned. The review costs nothing and commits you to nothing.

The treatment has three names. Interventional radiologists say TARE, the trials call it selective internal radiation therapy or SIRT, and patients search for Y-90, so the title of this page, TARE Treatment - Transarterial Radioembolization, carries the two that are searched most. All three mean the same procedure. What follows explains how it works, which liver tumors it treats, what the randomized trials showed and failed to show, and how a patient from abroad fits the two required visits into one trip.

What TARE is, and why it takes two visits

Liver tumors feed almost entirely from the hepatic artery, while the healthy liver draws most of its blood from the portal vein. The whole treatment rests on that difference. Microspheres released into the artery flow preferentially into the tumor, lodge in its smallest vessels, and deliver beta radiation that travels only a few millimeters, so the tumor receives a dose that would be impossible to give from outside the body while the surrounding liver receives far less. Yttrium-90 has a half-life of 64 hours. Nearly all of its energy is spent within two weeks. The beads stay in place for good and do no harm.

The first visit maps, the second treats. Before any microspheres are given, a catheter study of the liver arteries is done and a tracer, technetium-labeled albumin particles of the same size as the beads, is injected to see where they would go. A scan then shows how much would escape to the lungs and whether any would reach the stomach or bowel, and a nuclear medicine physicist calculates the dose from the images. Treatment follows one to three weeks later, on a second catheter visit, with the dose adjusted to what the mapping showed.

At Biruni Hospital the mapping and the treatment are done by the interventional radiology team with nuclear medicine, and the patient is assessed beforehand at a liver tumor board with the hepatologists, surgeons and medical oncologists who deliver the alternatives on the same site. Chemotherapy, where it is part of the plan, is given by the medical oncology team in the same building.

Who it is for

Four groups of patients account for nearly all radioembolization, and the aim differs in each.

Liver cancer that cannot be removed, a single tumor
Hepatocellular carcinoma of up to eight centimeters in a liver that still works well, in a patient who cannot have surgery or is waiting for a transplant. Here the dose can be planned at an ablative level to a single segment, and the aim is to destroy the tumor or to hold it in check until a transplant. This is the group with the best results.
Liver cancer that has grown into the portal vein
Tumor in the portal vein rules out chemoembolization, because blocking the artery would leave the liver with no blood supply. Radioembolization does not block the artery, so it remains possible. The randomized trials in this group compared it with sorafenib tablets and found the same survival with far fewer side effects.
Bowel cancer metastases in the liver after first-line chemotherapy
Patients whose liver metastases have grown despite first-line chemotherapy, in whom radioembolization added to second-line chemotherapy delayed progression in the liver. Survival was not improved in the trial, and the page says so below.
Preparing the liver for surgery
In selected patients, treating one lobe with radioembolization shrinks the tumor and makes the untreated lobe grow, so that a surgeon can later remove the diseased lobe and leave enough liver behind. This use is planned with the liver surgeon from the start.

Poor liver function rules it out, since a Child-Pugh class beyond A or a raised bilirubin means the healthy liver cannot absorb the dose it will receive. So does a mapping scan showing that more than a set fraction of the beads would reach the lungs, when disease outside the liver dominates the picture, or when a patient is too unwell to lie on an angiography table for two hours.

What the trials found, and what they did not

In advanced liver cancer, no longer life than tablets, and a much easier life

SARAH and SIRveNIB, two randomized trials against sorafenib
SARAH randomized 459 patients in France with locally advanced liver cancer to radioembolization with resin microspheres or to sorafenib tablets. Median survival was 8.0 months with radioembolization and 9.9 with sorafenib, a difference that was not statistically significant. Severe treatment-related fatigue affected 9 percent against 19 percent, severe diarrhea 1 percent against 14 percent, and hand-foot skin reaction under 1 percent against 6 percent. Vilgrain and colleagues, Lancet Oncology, 2017. SIRveNIB randomized 360 patients in eleven Asia-Pacific countries the same way. Median survival was 8.8 against 10.0 months, again not significantly different, and severe side effects occurred in 27.7 percent with radioembolization against 50.6 percent with sorafenib. Chow and colleagues, Journal of Clinical Oncology, 2018. In both trials a fifth to a quarter of patients assigned to radioembolization never received it, because the mapping visit found a reason not to proceed.

The dose, and the patient, decide

DOSISPHERE-01 and LEGACY
The negative trials used a standard dose to the whole treated lobe. DOSISPHERE-01 randomized 60 patients with large liver cancers to that standard dose or to a personalized dose of at least 205 gray aimed at the tumor itself. The tumor responded in 71 percent of patients with personalized dosing against 36 percent with the standard, and serious adverse events were fewer, 20 against 33 percent. Garin and colleagues, Lancet Gastroenterology and Hepatology, 2021. LEGACY then looked at 162 patients with a single unresectable liver cancer of up to eight centimeters, a median of 2.7, treated with glass microspheres at ablative doses to a small part of the liver. Independent reviewers found a response in 88.3 percent, lasting six months or more in 62.2 percent, and three-year survival was 86.6 percent overall and 92.8 percent among the 45 patients who went on to transplant or resection. Salem and colleagues, Hepatology, 2021. The lesson of the four studies together is that radioembolization works best as a high-dose treatment aimed at a defined tumor in a liver that can spare it, and least well as a lobe-wide treatment for advanced disease.

In bowel cancer metastases, more time before the liver progresses, no more time overall

EPOCH, radioembolization added to second-line chemotherapy
EPOCH randomized 428 patients from 95 centers whose colorectal liver metastases had progressed on first-line chemotherapy to second-line chemotherapy with or without radioembolization. Progression in the liver was delayed, with a median of 9.1 months against 7.2, and the tumor responded in 34 percent against 21 percent. Overall survival was 14.0 months against 14.4, no different. Grade 3 adverse events were more frequent with radioembolization, 68.4 against 49.3 percent. The authors called for further work to define who benefits. Mulcahy and colleagues, Journal of Clinical Oncology, 2021.

The two procedures, step by step

Consultation and tumor board
Scans, liver function and the history are reviewed, and the board confirms that radioembolization is the right choice and whether the aim is cure, control or preparation for surgery. Blood thinners are paused on the schedule your own doctor sets.
Mapping angiography
Under local anesthetic and light sedation, a catheter enters the artery at the wrist or groin and is guided into the liver. The arteries are mapped, small vessels running to the stomach or bowel are blocked with coils where needed, and the tracer is injected. One to two hours on the table and a few hours of observation.
Dosimetry
A scan of the tracer shows the fraction reaching the lungs and the distribution within the liver. The physicist and the radiologist calculate the activity of yttrium-90 needed for the planned dose to the tumor and the safe dose to the healthy liver. A lung fraction above the limit ends the plan, which is the reason a minority of patients do not go on to treatment.
Treatment
One to three weeks later, by the same route, the catheter is placed in the artery that the mapping identified and the microspheres are infused slowly over several minutes. A scan afterward confirms where they lodged. Most patients stay one night and leave the next day.
The first weeks
Tiredness, a dull ache under the ribs, mild nausea and a low fever for one to two weeks are expected and come from the radiation working. Pain relief and anti-sickness tablets cover them. For two to three days the patient keeps a little distance from small children and pregnant women, and the treatment summary explains the reason.

Risks and side effects

Most side effects come from the radiation working. The serious ones come from beads in the wrong place.

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

Complications of radioembolization
Complication How common What is done
Post-radioembolization syndrome, which is fatigue, ache, nausea and low fever The majority, for one to two weeks Tablets, rest, and it passes
Radiation damage to the liver, with jaundice and fluid in the abdomen weeks later A few percent, more with poor liver function or a lobe-wide dose Prevented by patient selection and dosimetry. Treated with steroids and supportive care
Ulcer in the stomach or duodenum from beads that strayed Uncommon since coiling of side vessels became routine Acid suppression, endoscopy, and time
Radiation inflammation of the lung Rare, and prevented by the lung fraction limit at mapping The reason treatment is withheld when the shunt is large
Inflammation of the gallbladder Occasional Antibiotics, rarely removal
Bleeding or bruising at the puncture site Common and minor Pressure and rest
Contrast allergy or kidney strain from the dye Rare Screening beforehand, fluids

Severe side effects were fewer with radioembolization than with sorafenib in both randomized trials, and more frequent than with chemotherapy alone when it was added to chemotherapy. Read that as a treatment that is easier than tablets in advanced disease and adds its own burden when combined with drugs.

TARE, TACE, ablation and drugs

Radioembolization or chemoembolization
Chemoembolization, TACE, blocks the tumor's artery with beads that carry a chemotherapy drug and starves it. It is the older and more widely available treatment for intermediate-stage liver cancer and is repeated several times. Radioembolization leaves the artery open, delivers radiation instead of a drug, is usually given once, causes less pain and fever afterward, and remains possible when tumor sits in the portal vein. Trials comparing the two head to head have shown similar survival with less time in hospital after radioembolization.
Radioembolization or ablation
Microwave or radiofrequency ablation treats tumors under three centimeters through a needle in one session with a curative aim and is preferred for them. Radioembolization treats larger tumors, several tumors in one lobe, or tumors that a needle cannot reach safely.
Radioembolization or drugs
Sorafenib, lenvatinib and the newer immunotherapy combinations treat the whole body and are the standard for advanced liver cancer. Radioembolization treats the liver only, matched sorafenib on survival with fewer side effects in two trials, and is increasingly combined with drugs in trials. For bowel cancer metastases the drugs come first and radioembolization is added to them.

Days in Istanbul, cost and the trip

Two visits or one long one. The table sets out both.

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How long to plan for
Option What happens Time in Istanbul
Two visits, separated Mapping on a first visit of three to four days, treatment on a second visit of four to five days one to three weeks later Two trips, total seven to nine days
One trip, both procedures Mapping in the first week, the wait for dosimetry and microsphere delivery, treatment in the second or third week Twelve to eighteen days
Both lobes, staged Treatment of the second lobe four to eight weeks after the first A third visit of four to five days

Each dose of microspheres is ordered for a named patient at a set activity and a set date. The two procedures therefore cannot fit into one week. Cost depends on the microspheres, which are the largest item and are priced per dose, on whether one or two lobes are treated, on the mapping study with its coils and tracer, on the angiography and the night in hospital, and on the imaging before and after. Published packages in Istanbul cover the consultation, the mapping, the dosimetry, the treatment with the microspheres, one night, the follow-up scan, an interpreter and transfers, and leave out the hotel, flights, chemotherapy and the treatment of a complication. Liver function, kidney function and blood thinners change the plan. A figure follows the review of your scans and blood tests, and that review is free. One coordinator handles the case from the first message, in English, Arabic, French, Russian, Serbian, Romanian or Spanish, or through an interpreter, sends the appointment confirmation and an invitation letter naming the hospital and the treating doctor ten days before travel, and books the hotel and the transfers for each visit. The room has a companion bed. Halal, vegetarian and diabetic meals are available, a prayer room is on site, and a female doctor can be requested when you first write. You can fly two days after either procedure.

Results, and after you fly home

The response takes time to show. Doctors take the first MRI or CT at three months, since the treated tumor swells before it shrinks and an earlier scan misleads, and scans then continue every three months for the first year. Liver function gets checked at two, four and eight weeks. Once you are back home the discharge file tells your oncologist how to continue. The coordinator stays reachable on the same WhatsApp number, with clinical questions passed to the treating radiologist.

  1. Liver blood tests at two, four and eight weeks, sent to your own doctor
  2. MRI or CT of the liver at three months, then every three months in the first year
  3. A tumor marker with each scan, alpha-fetoprotein for liver cancer or CEA for bowel cancer
  4. Chemotherapy or targeted drugs continued at home where the plan includes them
  5. A local doctor the same day for jaundice, swelling of the abdomen, black stools, vomiting blood, fever above 38.5 degrees after the second week, or breathlessness

TARE Treatment - Transarterial Radioembolization FAQ

Is TARE a cure for liver cancer?
For a single unresectable liver cancer treated with an ablative dose, it can be. In the LEGACY study 88 percent of tumors responded and 87 percent of patients were alive at three years, and some went on to transplant or surgery. For advanced disease it controls the liver and matched sorafenib on survival, and for bowel cancer metastases it delays progression in the liver without lengthening life overall.
Why do I need two procedures?
The first is a mapping angiography with a tracer that shows where the microspheres will go and how much would reach the lungs. The dose is calculated from it, and the microspheres are ordered for you at that activity. The treatment follows one to three weeks later by the same route.
Am I radioactive after TARE?
Very slightly, for a few days. Yttrium-90 emits beta radiation that travels millimeters, and nearly all of it is spent within two weeks. Keeping a little distance from small children and pregnant women for two to three days is the only precaution.
How does TARE compare with TACE?
Chemoembolization blocks the artery and delivers a drug, is repeated several times and causes more pain and fever afterward. Radioembolization leaves the artery open, delivers radiation, is usually given once, and remains possible when tumor sits in the portal vein. Survival has been similar in comparisons.
How long do I stay in Istanbul?
Seven to nine days across two trips, or twelve to eighteen days in one trip that covers the mapping, the wait for the microspheres and the treatment. You can fly two days after either procedure.
What are the side effects?
Tiredness, a dull ache under the ribs, nausea and a low fever for one to two weeks in most patients. Radiation damage to the liver, an ulcer from stray beads and lung inflammation are uncommon and are the reasons for the mapping study and the dose calculation. Severe side effects were half as frequent as with sorafenib in a randomized trial.

References

  1. Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18(12):1624-1636.
  2. Chow PKH, Gandhi M, Tan SB, et al. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J Clin Oncol. 2018;36(19):1913-1921.
  3. Garin E, Tselikas L, Guiu B, et al. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(1):17-29.
  4. Salem R, Johnson GE, Kim E, et al. Yttrium-90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study. Hepatology. 2021;74(5):2342-2352.
  5. Mulcahy MF, Mahvash A, Pracht M, et al. Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial. J Clin Oncol. 2021;39(35):3897-3907.

Editor's note

Written by the Biruni Hospital medical editorial team. Reviewed by Assistant Professor Yunus Emre AKPINAR, Radiology.

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