Oncology
Procedure Guide
Early HCC (BCLC A) not amenable to resection, particularly if not amenable to ablation as well.
Intermediate to advanced HCC (BCLC B-C) with preserved liver function including those with tumor thrombus.
INR >1.5, Plts <50K, or other uncorrected coagulopathy
Immediately life-threatening extrahepatic dx
20% lung shunt function, 30 Gy per session or 50 Gy for life particularly if poor pulmonary reserve (glass); 30 Gy limit (resin)
More likely w/ tumor thrombus or evidence of arteriovenous/portal shunting
Tumor burden >50% w/ albumin <3 mg/dl
AST/ALT 5xs upper limit
Pregnancy
(Relative) bilirubin >2 mg/dl, creatinine >2.5 mg/dl, ECOG >2, biliary obstruction
NOTE: Some data suggests benefit for carefully selected patients with more advanced disease (BCLC C-D) with median survival as high as 19.6 mo and some patients downstaged to transplant. However, patients with vascular invasion, metastases, high ECOG, and CP C only survived a few months.
Ablation vs TARE:
Debated, classically surgical resection or ablation thought to be ideal for solitary lesion <3 cm, but TARE studies starting to show similar outcomes with radiation segmentectomy and doses ~400 Gy.
Advantage of TARE is avoiding the low risk of ablation tract seeding if trying to bridge to transplant and treatment of lesions not amenable to ablation. However, ablation is less expensive and can be more efficient.
TACE vs TARE:
Debated but recent studies suggest TARE is likely superior to TACE at least for HCC.
PREMIERE study: TACE vs TARE TTP 6.8 vs >26 mo; median OS 17.7 vs 18.6 mo
TRACE study: TACE vs TARE TTP 9.5 vs 17.1 mo; median OS 15.6 vs 30.2 mo; AE similar 39 vs 53% (p=0.47)
TARE is a “microembolic”, 20-60 um, resulting in less post embolization syndrome in some studies vs TACE which uses larger particles. However, TARE has the unique risk of radiation induced liver injury.
The superiority of TARE is less clear for hepatic metastases. Examples below.
This meta-analysis of TACE vs TARE for NET mets showed similar progression free survival and complications (6.9% vs 8.5%). OS ranges of 17-82 mo vs 14-67 mo.
CRC mets: DEBIRI TACE + chemo 0S 19 mo; TARE OS 9.6-10.6 mo
TARE vs chemotherapy:
TARE vs sorafenib for HCC: mixed data, initial sorafenib trials (e.g. SHARP) had median OS 8.1 mo, which is less than many TARE studies BUT two prospective studies showed similar OS but better local control and less adverse events with TARE
SARAH and SORAMIC trials: better survival benefit with sorafenib for patients <65yo, absence of cirrhosis, non EtOH etiology of cirrhosis, CP A, no previous LDT, and lower ALBI score for advanced HCC
CRC mets
FOXFIRE, SIRFLOX, FOXFIRE-Global trials: TARE improves local control but not PFS or OS when combined with 1st line chemo
EPOCH trial: TARE + 2nd line chemo > chemo alone; PFS 8.0 v 7.2 mo, hPFS 9.1 v 7.2 mo, not OS but not designed to assess this
Dosimetry:
Generally, high tumor doses can function like an ablation with great results but this has to balanced with the volume of normal liver being treated and lung shunt fraction.
TARGET study: Higher tumor dose associated with better survival and AFP response. No association between normal tissue dose and grade 3 or higher hyperbilirubinemia.
LEGACY trial: RCT with solitary unresectable HCC <8 cm. Radiation segmentectomy resulted in 3 yr survival 86%, ORR 88%, and 100% complete pathologic necrosis for tumors receiving >400 Gy.
DOSISPHERE-01 trial: personalized dosimetry superior to standard in terms of local control and survival
LASER trial: 83% complete response with radiation segmentectomy for BCLC A
MRI or triphasic CT to characterize anatomy and measure liver volumes
Obtain PT/INR, CBC, AFP, and CMP.
Assess functional status, liver function, and severity of disease, e.g., ECOG, CP, ALBI, and BCLC.
Some premedication with Zofran 16 mg IV and Protonix 40 mg IV
If treating CRC mets, should hold Avastin 4 wks prior and after and reduce oxaliplatin to 60mg/m2 for three cycles. See this multidisciplinary consensus on the safety of TARE with various systemic anticancer agents.
Mapping (Part 1):
Obtain common femoral or radial access. Some recommend alternating femoral access for mapping vs treatment, e.g., left femoral for mapping and right femoral for treatment so access is closer to table for delivery.
Select arteries to evaluate with base 4-5 Fr catheter pending preprocedure imaging. Often the common hepatic artery +/- other arteries for variant anatomy or to assess for parasitized tumor supply.
Common catheters include the C2 and Simmons 1. Some use an RH catheter for women with smaller aorta and more acute origin of the celiac. Mikaelson often works well for the left gastric and right inferior phrenic.
Up to 50% of patients will have variant hepatic arterial anatomy. Common examples include replaces or accessory right or left hepatic arteries arising from the SMA or left gastric, respectively.
Common parasitized vascular supply to consider. More common after previous treatment.
Right superior/dome lesions - right inferior phrenic
Right inferior tumors - suprarenal/capsular branches of the right renal artery, omental, and supraduodenal arteries
Left tumors - gastric arteries and internal mammary
Lots of variation in approaches. The important thing is to be systematic to map out the target tumor supply, volume(s) to be treated for dosimetry, and potential collaterals/variants to avoid non-target embolization.
Some start with an abdominal aortogram if concerned about parasitized vascular supply.
Most obtain a run from the common hepatic artery in AP and 30* RAO to lay out the hepatic vascular anatomy to use as a roadmap (e.g. 3 mL for 12 mL or 15 mL). Many will also do a cone beam CT.
Use a microcatheter and wire (e.g. ProGreat and fathom) to further select individual branches to further map out the tumor supply and determine a site for delivery that will fully cover the target tumor(s) while minimizing the dose to normal parenchyma. Often people will perform both runs and cone beam CTs for target branches.
(Optional) Embolization, often using coils, of non-dominant branches feeding the tumor to redirect supply from the vessel(s) planned for delivery. Can also embolize collaterals/variants arteries supplying extrahepatic structures downstream of the planned delivery site to avoid non-target embolization.
Common collaterals/variants to avoid embolizing. Look for unique flow dynamics to identify, e.g., persisting on delay due to different capillary filling pressures.
From the right hepatic arteries - cystic artery, supraduodenal arteries
From the left hepatic arteries - accessory gastric or esophageal, left phrenic, falciform artery
(Optional) Chemoembolization for smaller non-dominant tumors.
Deliver Tc99m-macroaggregated albumin (MAA), ideally from the location of planned delivery.
Some institutions do same day mapping and delivery and send the patient to nuclear medicine with microcatheter still in place. Most remove catheters/sheath, get hemostasis, send to nuc med, and have the patient come back a different day to order dose accordingly.
Dosimetry:
Glass microspheres (Therasphere) dosing was originally based on treatment volume (MIRD model), but does not account for actually tumor volume. Resin microspheres (SIRspheres) dosing was originally based on body surface area and tumor to liver volume ratio (BSA model), which is vulnerable to mismatch between patient size and actual liver volume (e.g. obesity or hepatomegaly)
Personalize dosimetry or a partition model are likely superior to calculate tumor, non-tumor treated, and non-tumor non-treated volumes and doses.
Generally three approaches with different dosing:
Traditional lobar dosing for widespread multi-focal disease
Radiation segmentectomy with ablative dose for early stage disease as definitive treatment or downstage for transplant
Subablative lobar or larger area treatment with “boost” or more ablative dose to smaller area for advanced stage disease
Limits:
Max of 2 segments per treatment for radiation segmentectomy. Try to leave at least 30% of liver untreated.
20% lung shunt
30 Gy per session or 50 Gy for life (TheraSpheres), 30 Gy (SIRSpheres)
Risk of Radiation Induced Liver Injury (RILI)
>40-100 Gy to normal liver (max tolerable dose for cirrhotic v. non-cirrhotic liver = 70 v. 80 Gy).
Certain chemo potentiates Y90 effects [gemcitabine and capecitabine (Xeloda)] or makes the liver more sensitive to toxicity by being hepatotoxic themselves (oxaliplatin, paclitaxel)
TheraSpheres (glass): less embolic and hotter, approved for HCC, dose calculator
Ordering: specific dose calibrated on Sunday 12:00 ET, second week dose would have more particles for big area
Target dosing: >400 Gy for segmentectomy, >205 Gy to targeted tumor and 140-150 Gy to surrounding tissue for lobar, >205 Gy to targeted tumor and 120 Gy to surrounding tissue for whole liver
SIRSpheres (resin): more embolic and less hot, used for mets more than HCC
Ordering: Same amount delivered regardless and pipetted out
Target dosing: >250 Gy for segmentectomy, >170 Gy to targeted tumor and 100-120 Gy to surrounding tissue for lobar, >100-120 Gy for whole liver
Options For High Shunt Fraction:
Ward et al estimates 89% can still be treated using combination of the techniques below.
Bland/TACE to reduce via Embospheres 500-700 um NOT to stasis as it may prevent future TARE followed by TARE in 10-14 days
Low-dose or segmental TARE.
Balloon occlusion of treatment side and middle hepatic veins prior to TARE until 1-5 min after, e.g. 5.5 Fr Fogarty via two 6 Fr IJ sheaths with aspiration prior to deflation.
Embolization of competing outflow veins in the setting of hepatofugal portal flow.
Systemic chemo for 8-12 wks followed by repeat mapping.
Delivery (Part 2):
Obtain femoral or radial access. Some recommend alternating femoral access for mapping vs treatment, e.g., left femoral for mapping and right femoral for treatment.
Re-select the target vessel(s) for delivery with base catheter and microsystem of choice.
Ideally when possible to deliver through a larger microcatheter.
Newer data suggests that Pressure-Enabled Drug Delivery (PEDD) microcatheters (e.g. TriNav) increases tumor delivery where lobar PEDD gives similar tumor delivery to more selective delivery with an end hole catheter.
Confirm catheter positioning and flow with DSA.
Hook up Y90 and infuse. With Resin beads or smaller targets may need to assess intermittently for stasis. If sluggish flow, pause 1-2 min and reassess.
Treatment of cystic artery likely safe - reports of some pain during injection and after, 50% had GB wall thickening on 1 month follow up CT
Flush microcatheter with 20 mL syringes of D5W prior to removal.
Discard catheter and repeat with new microcatheter if performing other treatments
Remove sheath and obtain hemostasis
Post-embolization syndrome (~20%): less common than TACE due to being less embolic (20-60 um beads), ab pain, fever, nausea, fatigue -> often self-limited by 10 days
Hepatic decompensation if Child Pugh B or ECOG 2
Radioembolization-induced liver disease (REILD, <2%): Tbili >3 mg/dL, variable alk phos, and minimal changes in transaminases, 1-2 mo post-treatment
Gastritis or ulcers (1-2%): double PPI/protonix dose and give carafate, solumedrol may help too, often lasts 4-10 mo even with treatment
Radiation pneumonitis (<<1%, only case reports): occurs 1-6 mo after treatment, increased risk if lung shunt >10%, particularly if >20%
Cholecystitis (1%), hematoma, pseudoaneurysm
No prolonged contact w/ kids or pregnant women for 3d
Pt need to stay well-hydrated
Discharge with methylpredisolone tapered dose pack, oxycodone 5 mg q6h PRN, Protonix 40 mg/d, Zofran 4 mg q6h PRN
Common to have abd/should/back pain, fatigue, nausea, anorexia, and fever up to 101*F, peaking at 2-3 d and lasting 1-2 wks.
Check in within 1-2 wks
Repeat labs and CE-MRI in (4-6wks, some skip), 3mo, 6mo, 1yr
mRECIST criteria: measures only enhancing tumor, (CR) no enhancement, (PR) >30% decrease, (PD) >20% increase, (SD) inbetween