PATIENT SELECTION AND EVALUATION

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3. Patient selection and SIRT planning should be decided by a multidisciplinary team comprised of surgeons, interventional radiologists, hepatologists, oncologists, radiation oncologists, and nuclear medicine specialists.

References

Article

Grade

Key Points

Fong and Tanabe. The Clinical Management of Hepatocellular Carcinoma in the United States, Europe, and Asia: A Comprehensive and Evidence-Based Comparison and Review. Cancer 2014 Sep 15;120(18):2824-38, doi: 10.1002/cncr.28730

Guidelines

  • Review of 3 clinical practice guidelines: NCCN, EASL–EORTC, and AOS
  • They are fairly similar, with variances in surveillance and treatment due to regional variations in disease
  • Diagnostic criteria remains controversial, especially for lesions <1 cm
  • EASL-EORTC uses BCLC staging; NCCN uses resectability; and AOS uses determinants of survival
  • Recommended treatment in all 3 is sorafenib for HCC that is not amenable to resection, ablation, or transplantation with well preserved liver function
  • A multidisciplinary team that includes surgeons, medical oncologists, hepatologists, radiologists, and pathologists is key in management of patients with HCC
Song et al. The management of hepatocellular carcinoma around the world: a comparison of guidelines from 2001 to 2011. Liver Int 2012 Aug;32(7):1053-63, doi: 10.1111/j.1478-3231.2012.02792.x

Guidelines

  • Systematic review of 17 clinical practice guidelines which used diagnostic algorithms that were either size-based, non-size-based, or had no detailed criteria
  • Diagnosis can be carried out by imaging, serological tests, and histology, the latter being the one with least differences between guidelines
  • Guidelines differ regarding the appropriateness of candidates for surgery
  • Interval for surveillance differs between guidelines
  • The participation of a multidisciplinary team including hepatologists, pathologists, radiologists, surgeons and oncologists is recommended by 3 of the guidelines
Cheng et al. Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition). Liver Cancer 2020;9:28–40, doi: 10.1159/000503685

C-EO

  • Doctors in China tend to use more curable treatments for PVTT patients 
  • PVTT should be diagnosed with Cheng’s classification
  • Different multidisciplinary treatments are recommended taking into account liver function (Child–Pugh), resectability, extrahepatic metastasis, and extent of PVTT
  • Surgery is the preferred option for patients with type I/II PVTT. Type III can undergo resection after downstaging with TACE and/or radiotherapy
  • SIRT is recommended for patients with unresectable primary tumors; PVTT types I–III; and Child–Pugh A liver function

4. The criteria used for selecting patients eligible for curative treatment after tumor downstaging should be the same as before tumor downstaging.

5. 18F-FDG PET/CT should be obtained prior to SIRT when available to determine baseline function.

References: SIRT with resin microspheres in non-Asian regions

Article

Grade

Key Points

Kucuk et al. Prognostic importance of 18F-FDG uptake pattern of hepatocellular cancer patients who received SIRT. Clin Nucl Med. 2013 Jul;38(7):e283-9. doi: 10.1097/RLU.0b013e3182867f17

B-NR

  • Retrospective single-center cohort study conducted in Turkey using resin microspheres
  • Analysis of 19 patients who underwent 18F-FDG PET/CT before SIRT treatment
  • Etiology not specified
  • Patterns of FDG uptake were significantly correlated with progression-free survival (PFS). Median PFS for patients with hypoactive liver tumors was 5.25 ± 1.52 months, 12.3 ± 2.6 months for patients with nonhomogeneous FDG uptake, and 19.8 ± 5.0 months for patients with focal intense uptake (P=0.017)
  • HCC patients with higher SUVmax lesions showed better PFS following SIRT treatment than patients with lower SUVmax lesions
Filippi et al. Decrease in total lesion glycolysis and survival after yttrium-90-radioembolization in poorly differentiated hepatocellular carcinoma with portal vein tumour thrombosis. Nucl Med Commun. 2018 Sep;39(9):845-852. doi: 10.1097/MNM.0000000000000879

C-LD

  • Retrospective single-center cohort study conducted in Italy using resin microspheres
  • Study aim was to evaluate the change in total lesion glycolysis (TLG) as a prognostic indicator for survival outcomes in HCC patients with PVTT after SIRT treatment
  • Retrospective analysis of 21 patients (33.3% HBV, 71.4% HCV, 9.5% HBV+HCV) with poorly differentiated HCC and PVTT who underwent SIRT. 18F-FDG PET-CT scans were taken at baseline and 1 month after SIRT treatment to assess decrease in total lesion glycolysis (ΔTLG) after SIRT
  • Mean overall survival was significantly longer for patients with ΔTLG > 50% (n=9) compared to patients with ΔTLG <50% (n= 12): 16.8 (95% CI  14.2-19.5) months and 7.5 (95% CI 6.5-8.6) months, respectively; p<0.001 [Table 3]
  • ΔTLG as assessed by 18F-FDG PET-CT scans may be a useful indicator for treatment response and outcomes in HCC patients with PVTT who undergo SIRT
Blanc-Durand et al. Signature of survival: a 18F-FDG PET based whole-liver radiomic analysis predicts survival after 90Y-TARE for hepatocellular carcinoma. Oncotarget. 2017;9(4):4549-4558. doi: 10.18632/oncotarget.23423

C-LD

  • Retrospective single-center case series conducted in Switzerland using resin and glass microspheres
  • Patient characteristics included unilobar (n=24) diffuse (n=18); PVI (n=21); serum AFP 17 kUI/L; BCLC A (n=3), B (N=18), C (n=26), Ascites (n=7); Child Pugh A (n=36), B (n=8); hepatitis B, C (n=17, 36.2%)
  • Administered activity 1.6 GBq
  • Average tumor volume was 170 cm3 and absorbed dose was 170 Gy
  • 30 patients recurred at median 6.9 months; 33 died of progression
  • Two difference methods were used to calculate risk related to PFS and OS and microsphere type did not affect survival using either calculation method
  • Pretreatment 18F-FDG PET independently predicts poor PFS and OS in patients undergoing SIRT for unresectable HCC

6. 99mTc MAA SPECT/CT should be used to study patient eligibility and dose.

References: SIRT with resin microspheres in Asian regions

Article

Grade

Key Points

Song et al. PET/CT-based dosimetry in 90Y-microsphere selective internal radiation therapy: Single cohort comparison with pretreatment planning on 99mTc-MAA imaging and correlation with treatment efficacy. Medicine (Baltimore). 2015;94(23):e945. doi: 10.1097/MD.0000000000000945

C-LD

  • Retrospective single-center (Korea) case series of patients with HCC (and other malignancies) treated with SIRT (resin microspheres)
  • Partition model (n=21) was used to calculate the injected activity (absorbed dose 2.1 BGq) except when the lung shunt fraction was high (>0.1), which used the BSA method (n=2) and reduced up to 40% according to manufacturer’s package insert (absorbed dose 1.7 BGq)
  • 99mTc SPECT/CT can be used as a conservative activity planning method
  • Stasis prevented full planned injected activity in 4 patients
  • PFS was 207 days, PFS was 286 days for patients with high absorbed dose (>200 Gy) and 92 days for patients with low absorbed dose (≤200Gy, P=0.046)
  • 90Y-PET-CT was effective method for post-SIRT dosimetry and prediction of treatment efficacy

Lau et al. Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys 2012 Jan 1;82(1):401-7, doi: 10.1016/j.ijrobp.2010.08.015

C-EO

  • Clinical consensus statement on use of resin microspheres for HCC patients
  • Most common activity calculation method is the empiric planning adjusted for body surface area
  • Delivered dose must be calculated for uninvolved, normal parenchyma (preferably <50 Gy). Some institutions in Asia have lower thresholds (40–43 Gy). If the uninvolved parenchyma is functionally impaired before SIRT, the maximal dose should remain <50 Gy and even <40 Gy
  • 99mTc MAA scanning should be carried out for every patient
  • Planning SIRT delivery must consider: safety thresholds for T/N ratio (lowest threshold of 2.0), lung shunt fraction, and parenchymal radiation exposure
  • BSA calculation should be used for all patients, regardless of application of partition model
  • Microsphere activity must be calculated for every administration. A very high initial dose may preclude further radioembolization

References: SIRT with resin microspheres in non-Asian regions

Article

Grade

Key Points

Vilgrain 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. doi: 10.1016/S1470-2045(17)30683-6

B-R

  • Multi-center open-label RCT conducted in France on SIRT (with resin microspheres) (with resin microspheres) vs sorafenib on locally advanced and unresectable HCC after unsuccessful TACE 
  • No significant difference in OS between SIRT and sorafenib
  • Compared sorafenib 400 mg twice daily with SIRT to lobe, sector or segment
  • Activity was calculated using BSA method
  • Patient characteristics included hepatitis C/B (SIRT, n=55/13; sorafenib, n=49/15); ECOG 0/1 (SIRT, n=145/92; sorafenib, n=139/83); BCLC A/B/C (SIRT, n=9/66/162; sorafenib n=12/61/149); Child Pugh A(5-6)/B7/unknown (SIRT, n=196/39/2; sorafenib, n=187/35/0); bilobar (SIRT, n=50; sorafenib, n=35); macrovascular invasion (SIRT, n=149; sorafenib, n=128); AFP (SIRT, median 87 ng/mL, sorafenib, median 80.0 ng/mL)
  • Calculation of the hepatopulmonary shunt fraction and tracer distribution was evaluated with 99Tc MAA SPECT imaging
  • Activity delivered per patient was 1.394 GBq
  • Median follow-up was 27.9 months in the SIRT group, 28.1 months in sorafenib group
  • Response was evaluated with RECIST 1.1
  • Median OS and PFS was 8.0 and 4.1 months for SIRT and 9.9 and 3.7 months for sorafenib
  • Best overall response include CR (SIRT, n=5; sorafenib, n=2), PR (SIRT, n=31; sorafenib, n=21), SD (SIRT, n=93; sorafenib, n=131), PD (SIRT, n=60; sorafenib, n=44)
  • 1088 serious adverse events were reported (SIRT, n=518 events; sorafenib, n=570 events)
Hermann et al. Relationship of tumor radiation-absorbed dose to survival and response in hepatocellular carcinoma treated with transarterial radioembolization with 90Y in the SARAH study. Radiology. 2020 Jun 30:191606. doi: 10.1148/radiol.2020191606

B-NR

  • Secondary analysis of SIRT patients from the multi-center (France) RCT of SIRT (resin) vs sorafenib
  • Liver function parameters for inclusion: bilirubin under or equals 50 µmol/L, AST or ALT under or equals 5 x ULN, INR under or equals 1.5
  • Tumor etiology: HBV (4% in dose-survival group, 5% in dose-tumor response group), HCV (23% in dose-survival group, 26% in dose-tumor response group)
  • For the dose-survival group, median OS was 9.3 months, median tumor radiation-absorbed dose was 112 Gy, median tumor volume as 152 cm3, median injected 90Y activity was 1342 mBq 
  • Median OS was 14.1 months for patients who had ≥ 100 Gy tumor radiation-absorbed dose, and 6.1 months for patients who had <100 Gy
  • Strong predictors of survival were ≥ 100 Gy tumor radiation-absorbed dose, ALBI grade of A1 and tumor burden ≤25%
  • No difference existed between tumor radiation-absorbed dose and objective response at 6 months, but participants who achieved disease control had median tumor radiation-absorbed dose of 121 Gy while participants with progressive disease this dose was 85 Gy (P=0.02)
  • Grade 1 and 2 fatigue occurred more often in participants who received ≥100 Gy tumor radiation-absorbed dose (P=0.05)
  • Longest survival and highest disease control rate were achieved when participants received ≥100 Gy with optimal agreement between 99mTc-MAA SPECT/CT and 90Y SPECT/CT or PET/CT
Ilhan et al. Predictive value of 99mTc-MAA SPECT for 90y-labeled resin microsphere distribution in radioembolization of primary and secondary hepatic tumors. J Nucl Med. 2015;56(11):1654-60. doi: 10.2967/jnumed.115.162685

C-LD

  • Retrospective single-center case series conducted in Austria and Germany using resin microspheres
  • Applied activity was calculated using BSA method; however, early cases (n=47) activity was adapted based on percentage of liver involvement
  • For HCC patients, mean tumor to background noise ratio differed between 99mTc-MAA SPECT and 90Y bremsstrahlung (P<0.01)
  • In general, visual grading of tracer distribution revealed lesions with high uptake on 99mTc-MAA SPECT and high update of 90Y microspheres during SIRT
Hartenbach et al. Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma. Clin Nucl Med. 2018 Jul;43(7):477-481. doi: 10.1097/RLU.0000000000002092

C-LD

  • Retrospective survival analysis (Germany) of 24 patients with intermediate stage HCC who underwent combined 99-mTc-MAA SPECT/CT and [18F]FEC PET/CT prior to SIRT treatment
  • A high tumor percentage of hypervascularized metabolically active tumor volume or vascularized tumor ratio (VTR), as assessed by combined 99-mTc-MAA SPECT/CT and [18F]FEC PET/CT, was significantly correlated with survival (hazard ratio, 11.65; 95% confidence interval, 1.62–83.73; P = 0.015)
  • Patients with higher tumor vascularization had lower median survival compared to patients with lower tumor vascularization: 274 ± 80 days vs 585 ± 284 days, respectively (P = 0.015)
  • HCC patients with high tumor vascularization in metabolically active areas, as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT, represent an unfavorable subgroup with reduced overall survival after SIRT treatment

7. T:N ratio should be obtained using 3D planning models or, alternatively, application of a voxel-based dosimetric approach (ie dose-volume histograms).

References: SIRT with resin microspheres in Asian regions

Article

Grade

Key Points

Wang et al. Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: From clinical aspects to dosimetry. PLoS One. 2018;13(1):e0190098. doi: 10.1371/journal.pone.0190098

C-LD

  • Retrospective single-center (Taiwan) case series 22 patients with unresectable HCC treated with EBRT after receiving SIRT (resin)
  • Patient characteristics include ECOG 0/1/2 (n=4/16/2) before EBRT, treatment naïve (n=4), prior treatment, including surgical resection, RFA, TACE and chemotherapy (n=18); chronic hepatitis B/C/B+C (n=17/2/2); Child Pugh A prior to SIRT (n=22)
  • SIRT was segmental (n=19) or whole liver (n=3)
  • Mean activity administered was 1.50 BGq; tumor absorbed dose was 115.8 Gy and dose to liver was 39.6 Gy
  • 3D biological effective dose distribution of EBRT and SIRT was generated, which is crucial for evaluating efficacy and toxicity
  • Mean days between SIRT and EBRT was 214 days
  • Mean prescribed dose of EBRT was 42.3 Gy in 14 fractions and targeted residual tumor (n=12), PVT (n=11, 6 should improvement after EBRT), and perihilar lymphadenopathies (n=4)
  • Actual delivered mean target and normal liver absorbed dose of EBRT was 42.3 Gy and 11.7 Gy; 3 patients did not complete RT
  • 1-, 2-, and 3-year overall survival at were 59.8%, 47.9%, and 47.9%
  • Median OS was 477 days. Median survival for Child Pugh A prior to EBRT was better than for Child Pugh B or C (P=0.01)
  • Tumor response 3 months after EBRT included PR (n=5), CR (n=4), PD (n=6) and new lesions were found in 7 patients
  • >Grade 2 liver toxicities developed in 8 patients; Grade 5 liver failure toxicity occurred in 5 patients
  • 7 patients had chronic hepatitis B infection and 1 had B+C; 6 were treated with antivirals, 1 had persistent low HBV titers
Lau et al. Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys 2012 Jan 1;82(1):401-7, doi: 10.1016/j.ijrobp.2010.08.015

C-EO

  • Clinical consensus statement on use of resin microspheres for HCC patients
  • Most common activity calculation method is the empiric planning adjusted for body surface area
  • Delivered dose must be calculated for uninvolved, normal parenchyma (preferably <50 Gy). Some institutions in Asia have lower thresholds (40–43 Gy). If the uninvolved parenchyma is functionally impaired before SIRT, the maximal dose should remain <50 Gy and even <40 Gy
  • 99mTc MAA scanning should be carried out for every patient
  • Planning SIRT delivery must consider: safety thresholds for T/N ratio (lowest threshold of 2.0), lung shunt fraction, and parenchymal radiation exposure
  • BSA calculation should be used for all patients, regardless of application of partition model
  • Microsphere activity must be calculated for every administration. A very high initial dose may preclude further radioembolization

References: SIRT with resin microspheres in non-Asian regions

Article

Grade

Key Points

Mañeru et al. Dosimetry and prescription in liver radioembolization with 90Y microspheres: 3D calculation of tumor-to-liver ratio from global 99mTc-MAA SPECT information. Phys Med Biol. 2017;62(23):9099-9111. doi: 10.1088/1361-6560/aa9536

C-LD

  • Retrospective case series conducted in Spain on HCC patients treated with resin microspheres
  • The 3D voxel matrix of SPECT to calculate T/N3D ratio was comparable to the Voxel S-value approach (VSV) method to calculate T/N ratio

8. Meticulous angiographic assessment of target areas requires the use of preprocedural CT angiography, cone beam CT (when available), power injection during DSA interrogation, microcatheterization, redistribution through selective arterial embolization and identification of situations where anatomical variations may result in non-targeted embolization.

References: SIRT with resin microspheres in Asian regions

Article

Grade

Key Points

Goh et al. Catheter-Directed Computed Tomography Hepatic Angiography for Yttrium-90 Selective Internal Radiotherapy of Hepatocellular Carcinoma Reduces Prophylactic Embolization of Extrahepatic Vessels. Cardiovasc Intervent Radiol. 2020 Mar;43(3):478-487. doi: 10.1007/s00270-019-02362-y

C-LD

  • Retrospective single-center (Singapore) case series analysis of 186 patients (41.4% HBV, 15.6% HCV, 1.6% HBV + HCV) who underwent catheter-directed computed tomography hepatic angiography (CD-CTHA) as part of SIRT treatment
  • Use of CD-CTHA in mapping of vascular anatomy is associated with a lower rate of selective prophylactic embolization than reported rates when digital subtraction angiography (DSA) is used (18.8% vs 36.8%, p<0.005)
  • CD-CTHA is associated with a low rate of complications and high technical success rate (99.5%) of SIRT treatment

References: SIRT with resin microspheres in non-Asian regions

Article

Grade

Key Points

Ertreo, et al. Comparison of Cone-Beam Tomography and CrossSectional Imaging for Volumetric and Dosimetric Calculations in Resin Yttrium-90 Radioembolization. Cardiovasc Intervent Radiology. 2018 Dec;41(12):1857-1866. doi: 10.1007/s00270-018-2030-0

C-LD

  • Retrospective single-center (USA) case series of 47 patients treated with SIRT (resin), 12 of them with HCC
  • CBCT-derived volumes were compared with perfused lobar volume derived from contrast-enhanced CT and MRI
  • The mean percentage difference between combined CT-MRI- and CBCT-derived calculated lobar volumes was 25.3% (p = 0.994). The mean percentage difference in calculated dose between the two methods was 21.8 ± 24.6% (p = 0.42)
  • Volume measurements derived from CT/MRI vs CBCT did not differ significantly, but there was variability between the 2 methods which led to differences in calculated dose

End of "PATIENT SELECTION AND EVALUATION"