Table 3 Clinical application of MRI in cancer-targeted therapy

From: Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

Technique

Drug

Target

Tumor

N

Results

References

DCE-MRI

Bevacizumab

VEGF

Breast cancer

70

Significant decreases in Ktrans, kep, Ve, and AUC60 after cycle 5 of treatment.

291PMID: 34298725

DCE-MRI

Bevacizumab (+chemotherapy)

VEGF

Breast cancer

19

Significant decreases in Ktrans, kep, and IAUGC at 180 s after cycle 1 of treatment. The median relative change in the slope of the wash-in curve from baseline to cycle 4 was significantly different between responders and nonresponders.

364PMID: 17709827

DCE-MRI

Bevacizumab (+chemotherapy)

VEGF

Breast cancer

21

Decreases in Ktrans, kep, and Ve after cycle 1 of treatment. No correlation with treatment response.

290PMID: 16391297

DSC-MRI

Bevacizumab (+radiotherapy)

VEGF

Glioblastoma

67

OS benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger baseline MRI contrast-enhancing tumors and for higher ADC.

300PMID: 32967939

DSC-MRI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

123

Quantitative DT1 showed a significant difference in OS at week 8 between responders and nonresponders/nonprogressors.

365PMID: 31248863

DSC-MRI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

254

Decreases in nrCBV, nrCBF, and nTMRO2 values after bevacizumab treatment. None of these parameters was predictive of OS.

302PMID: 32720870

DSC-MRI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

21

Early decreases in rCBV were predictive of improved survival.

303PMID: 25646027

DSC-MRI and DCE-MRI

Bevacizumab (+chemoradiation therapy)

VEGF

Glioblastoma

42

High pretreatment rCBV was predictive of improved OS.

305PMID: 32678438

DSC-MRI and DCE-MRI

Bevacizumab (+chemotherapy)

VEGF

Breast cancer

22

A lower ΔKtrans or ΔADC reduction in 21 days after treatment predicted shorter CNS-specific PFS. A lower ΔPeak or ΔIAUC60 reduction predicted shorter OS.

295PMID: 29770848

DSC-MRI and DCE-MRI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

33

PFS increased significantly with time to the maximum value of the residue (Tmax). OS decreased significantly with srCBV and increased significantly with Tmax.

366PMID: 33828310

MRS

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

13

Increased NAA/Cho at 8 weeks and decreased Cho/Cr and increased NAA/Cr and NAA/Cho at 16 weeks post-treatment was associated with both 6-month progression-free survival and 1-year survival.

317PMID: 23645534

MRS

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

21

A lower mI/c-Cr in the intratumoral and peritumoral volume before and during treatment was predictive of poor survival.

367PMID: 34751617

VHL and VAM

Bevacizumab

VEGF

Glioblastoma

13

Early response to bevacizumab was dominated by the reduction of smaller microvasculature.

326PMID: 28819189

DWI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

123

High pretreatment contrast-enhancing tumor volume was associated with shorter PFS and OS. A high volume fraction of increasing ADC after therapy was associated with shorter PFS, while a high volume fraction of decreasing ADC was associated with shorter OS.

301PMID: 25672376

DWI

Bevacizumab (+chemotherapy)

VEGF

Colorectal liver metastasis

74

Post-treatment ADCmean was significantly associated with OS and PFS.

312PMID: 35013857

DWI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

32

Pretreatment tumor volume was correlated with OS. Patients with high ADCL had favorable survival when treated with bevacizumab.

313PMID: 32365185

DWI

Bevacizumab (+chemotherapy)

VEGF

Glioblastoma

242

ADClow was an independent prognostic parameter for OS and PFS. Patients with ADClow ≥ 1241 × 10−6 mm²/s had prolonged OS compared with those with ADClow < 1241 × 10−6 mm²/s.

314PMID: 32393964

DCE-MRI and DWI

Bevacizumab (+chemotherapy)

VEGF

Colorectal liver metastasis

126

D-RECIST- but not RECIST-defined responders had significantly longer median DFS than nonresponders. D-RECIST- but not RECIST-defined responses independently predicted DFS.

310PMID: 33449175

APT MRI and DWI

Bevacizumab

VEGF

Glioblastoma

54

Mean APT signal intensity change after bevacizumab treatment indicated a low 12-month progression rate and longer PFS. High mean normalized CBV at follow-up was associated with a high 12-month progression rate and shorter PFS. Mean APT signal intensity change was a significant predictor of diffuse non-enhancing progression, whereas follow-up 95th percentile of the normalized CBV was a predictor of local enhancing progression.

323PMID: 32154775

CEST- EPI

Bevacizumab (with or without adjuvant chemotherapy or immunotherapy)

VEGF

Glioblastoma

11

The reduction in tumor acidity was linearly correlated with PFS, being a significant predictor of PFS.

322PMID: 30806888

DCE-MRI and FLAIR

Bevacizumab (+chemoradiation therapy)

VEGF

Glioblastoma

159

Increasing 2D-T1 and FLAIR post-treatment significantly predicted worse OS. Adjusting for 2D-T1 and treatment, increasing FLAIR represented a significantly higher risk for death.

368PMID: 29590461

FLAIR

Bevacizumab (with or without chemotherapy)

VEGF

Gliomas

33

Lower edge contrast of the FLAIR hyperintense region was associated with poorer PFS and OS.

369PMID: 29622553

DCE-MRI and FLAIR

Bevacizumab (with or without chemotherapy)

VEGF

Glioblastoma

119

Early MRI response could predict PFS and OS. Early MRI progression was a strong independent predictor of mortality.

370PMID: 28678383

T2WI and DCE-MRI

Bevacizumab (+chemoradiation therapy)

VEGF

Glioblastoma

232

At weeks 6 and 12 of treatment, increases in baseline necrosis and de novo necrosis were strongly associated with worse OS and PFS.

371PMID: 31076534

TME mapping

Bevacizumab

VEGF

Glioblastoma

18

Higher percentage of neovascularization and active tumor in baseline indicated poor or no treatment response.

329PMID: 30361791

PWI

Angiocept, bevacizumab, cilengitide, enzastaurin, sorafenib, thalidomide and vandetani

VEGF

Glioblastoma

117

Patients with an angiogenic subtype of glioblastoma benefited from antiangiogenic therapy with improved OS.

372PMID: 28007759

DCE-MRI and DWI

Bevacizumab or aflibercept or cediranib or cabozantinib

VEGF

Glioblastoma

258

Baseline ADCL was an independent predictive biomarker for OS in anti-VEGF therapies. An ADCL threshold of 1.24 μm2/ms produced the largest OS differences between patients.

309PMID: 28655794

DWI-MRI

Lenvatinib and toripalimab

VEGF

Intrahepatic cholangiocarcinomas

43

ADC was an independent variable associated with early progression. Patients with low ADC values showed shorter PFS.

307PMID: 35488518

Gd-EOB-DTPA-enhanced MRI

Lenvatinib or atezolizumab and bevacizumab

VEGF

Hepatocellular carcinoma

68

No predictive association between PFS and EOB-MRI in the lenvatinib group. In the atezolizumab plus bevacizumab group, the heterogeneous type and hyperintensity type had significantly shorter PFS than the homogeneous type and the hypointensity type, respectively.

332PMID: 35159095

DSC-MRI and DCE-MRI

Cabozantinib

VEGF

Glioblastoma

108

A log-linear association between baseline tumor volume and OS and a linear correlation between initial change in tumor volume and OS were observed. Continuous measures of baseline tumor volume and volumetric response were independent predictors of OS.

299PMID: 29660005

DSC-MRI and DCE-MRI

Lenalidomide or axitinib

VEGF

Hepatocellular carcinoma

74

Greater reductions in ΔPeak or ΔAUC on days 3 and 14, and ΔKtrans on day 14 were associated with better PFS. Greater reductions in ΔAUC or ΔKtrans on day 14 were associated with better OS. ΔKtrans on day 14 was an independent predictor of PFS after controlling for ORR and DCR.

296PMID: 34638446

ASL MRI

Sunitinib or pazopanib

VEGF

Renal cell carcinoma

28

Responders had higher baseline tumor perfusion than nonresponders. Interval reductions in perfusion at week 2, cycle 2, and cycle 4 were not associated with ORR or PFS.

327PMID: 33258745

DWI

Sunitinib, pazopanib or axitinib

VEGF

Renal cell carcinoma

92

Patients with >5 bone metastases (BM) on WB-DWI/MRI had a lower response rate, and more frequently suffered early progressive disease, shorter PFS, and shorter OS than patients with ≤5 BM.

373PMID: 32297532

DWI

Sunitinib

VEGF

Gastrointestinal stromal tumor

15

Pretreatment β and ΔD differed between good- and poor-responding lesions. Combining ΔD with pretreatment β obtained an improved AUC (0.843) with a predictive accuracy of 75.7%.

308PMID: 28643387

DCE-MRI and FLAIR

Sunitinib

VEGF

Renal cell carcinoma

34

Higher baseline and day 14 values for Ktrans were significantly associated with longer PFS.

374PMID: 29383520

DWI

Imatinib or sunitinib

VEGF

Gastrointestinal stromal tumor

62

The percentage change of ADC and longest diameter after 2 weeks of therapy were significantly different between responders and nonresponders.

306PMID: 30103713

DCE-MRI

Regorafenib

VEGF

Colorectal cancer

27

>70% drop in KEF (6/23) was associated with a higher disease control rate at 2 months and improved PFS and OS.

297PMID: 28790159

DCE-MRI

Sorafenib

VEGF

Hepatocellular carcinoma

29

Stratification according to mRECIST and vqEASL successfully captured response and stratified OS, while stratification according to RECIST and %qEASL did not correlate with OS.

298PMID: 33123796

Gd-EOB-DTPA-enhanced MRI

Sorafenib (with or without selective internal radiation therapy)

VEGF

Hepatocellular carcinoma

312

High gadoxetic acid uptake on pretreatment MRI was significantly associated with shorter OS.

375PMID: 34541612

Gd-EOB-DTPA-enhanced MRI

Sorafenib (with or without selective internal radiation therapy)

VEGF

Hepatocellular carcinoma

376

Peritumoral arterial enhancement and peritumoral hypointensity in hepatobiliary phase were predictors of worse OS. Peritumoral hypointensity in hepatobiliary phase was a predictor of liver decompensation.

376PMID: 34686780

Gd-EOB-DTPA-enhanced MRI

Sorafenib

VEGF

Hepatocellular carcinoma

65

Regular tumor margin and the presence of tumor thrombus were indicators of high RAF1 expression.

377PMID: 34738148

Gd-EOB-DTPA-enhanced MRI

Sorafenib

VEGF

Hepatocellular carcinoma

91

The presence of incomplete capsule or intratumoral vessels and the absence of capsule were potential indicators of high BRAF and RAF1 expression.

378PMID: 30547202

MRE

Sorafenib

VEGF

Hepatocellular carcinoma

50

Higher MRE-assessed liver stiffness was significantly associated with poor OS and significant liver injury after sorafenib therapy.

328PMID: 33033862

MRS

Cediranib (+chemoradiation therapy)

VEFG

Glioblastoma

40

Total Cho/healthy Cr after 1 month of treatment was significantly associated with OS.

379PMID: 29202103

IVIM-MRI and DCE-MRI

Lenalidomide

VEGF

Hepatocellular carcinoma

44

Participants with a higher slope, Kep and ADC values had longer PFS. Participants with small tumor size, higher slope, ADC and f values had longer OS. Kep and ADC were independent predictors of PFS. Slope and ADC were independent predictors of OS.

325PMID: 34441274

DCE-MRI

Bevacizumab and erlotinib

VEGF and EGFR

NSCLC

44

Whole-tumor Ktrans was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values after 3 weeks had shorter PFS.

200PMID: 21149474

DWI

Bevacizumab and erlotinib (+chemoradiation therapy)

VEGF and EGFR

Glioblastoma

36

A lower ADC percentile value within the T2-hyperintense lesion (T2L) at early follow-up timepoints was associated with worse outcomes. The ADC10% within the T2L at 2 months was strongly associated with OS and PFS.

315PMID: 25351579

DCE-MRI and DWI

Gefitinib (+radiotherapy)

EGFR

Nonsmall-cell lung cancer

253

Tumor regression rate, ADCpost, ΔADCpost, and ΔADCpost (%) were key imaging indicators for predicting the outcome.

311PMID: 34514171

DCE-MRI

Trastuzumab or T-DM1 ( + chemotherapy)

HER2

Breast cancer

46

Interim changes in ETV value were highly correlated with residual cancer burden.

380PMID: 29641224

DCE-MRI

Trastuzumab or/and pertuzumab

HER2

Breast cancer

21

Concentric tumor shrinkage pattern after targeted therapy was associated with pCR. No association between the initial enhancement ratio and pCR.

294PMID: 31444111

DSC-MRI

Trastuzumab (+chemotherapy)

HER2

Breast cancer

296

Patients with early rCR on MRI achieved pCR in 73% of HER2-positive breast cancer cases and 88% in the HR-negative subgroup. Achieving rCR was associated with a rate of the 5-year recurrence-free interval of 88%, compared with 68% without rCR.

381PMID: 28432515

IVIM-MRI

Nivolumab or pembrolizumab

PD-1

Non-small cell lung cancer (NSCLC)

20

An increased ADC at 8 weeks and decreased ADCkurt and ΔADCkurt 4 weeks after treatment were associated with objective responses and longer PFS. A decreased ΔADCskew at 4 weeks was associated with objective responses, disease control, and longer PFS and OS.

324PMID: 32203770

Gd-EOB-DTPA-enhanced MRI

Anti-PD-1/PD-L1 monotherapy

PD-1/PD-L1

Hepatocellular carcinoma (HCC)

18

The TTnP and median PFS in HCC patients with hyperintense nodules were significantly shorter than in those with hypointense HCC nodules after treatment.

331PMID: 34950184