Liver metastases: treatment planning

PJ Valette

Liver metastases removal December 2010 April 2011 : after chemotherapy

June 2011 : after resection of left lobe mets & portal embol.

Sept 2011 : 1 year after right Hepatectomy and CRC removal

Liver metastases removal

• Curative treatment of liver primary cancers or metastases can only be achieved by complete tumor removal: resection surgery and/or local ablation

• Neoadjuvant chemotherapy is used to reduce the size of lesions and to select responding patients before extensive surgery (CRC metastases - B Nordlinger)

• Combined treatments including portal embolization, arterial embolization, RF or microwave ablation before, after, or at the time of surgery may also be proposed

Liver metastases removal

• Such strategies are based on an individual treatment project – Involving several specialists: surgeon, radiologist, oncologist

– Including multiple steps

– With a sole objective: to remove all lesions

• Need for – A clear identification of each lesion: diagnosis, size, site

– A preliminary assessment of the feasibility of liver resection and/or tumor ablation: liver anatomy

– A complete description, step by step, of each treatment decided for each lesion: how, when, who ?

– A clear understanding of the results of the preoperative treatments

A 4 steps process

1. Diagnosis of cancer a) Detection and characterization

b) Assessment of extension

2. Treatment planning c) Therapeutic decision

d) Patient management

Therapeutic decision

• Hepatectomies are based on the

anatomical Couinaud segmentation

• Remnant liver should be

at least 30% of the functional liver

• Except for simple cases, resectability assessment needs:

– To determine the boundaries and volumes of each segment

– To localize tumors into segments

• Software aided liver segmentation and volume calculations

II

III IV

V

VIII

VI

VII I

The automatic segmentation • Based on the portal anatomy: represents the

real area of portal vascularization of each

branch but …

– The portal contrast enhancement needs to be

optimal for the automatic detection of the

venous tracks

– The branch to follow may be ambiguous in case

of trifurcations, anatomic variations, …

– Moreover: not really applicable at surgery

Rieker O (Rofo 2001): the automatic classification of

portal vein failed in 51 of 409 branches due to

unexpected anatomy

The semi-automatic segmentation

• Based on surgical anatomical landmarks

II

III IV

VII

VI

VIII

V

1) Liver surface

2) Perop. US

Gallbladder fossa

Umbilical fissure

Hepatic veins

Portal bifurcation

The semi-automatic segmentation

• Based on surgical anatomical landmarks

1. Inferior Vena Cava

2. Right hepatic vein

3. Gallbladder fossa

4. Umbilical fissure

5. Superficial ligmt venosum

6. Deep ligmt venosum

7. End of left portal vein

8. Right portal vein bifucation

9. Tip of left lobe

1

2

3 4

9

65

8

7

1

2

3 4

9

65

8

7

Liver volumes Tumor volumes

The liver analysis

The semi-automatic segmentation • Clinical evaluation of the concept

216 tumors into 48 patients

2 juniors (with software), 2 experts (without software), 1 adjudicator (expert + software)

1. Volume of sgmts: reproducibility ?

2. Segment localization of each tumor: accuracy ? • Juniors agreement: 89% (kappa 0,85)

• Experts agreement: 92% (kappa 0,88)

• Juniors vs Experts agreement: 97% (kappa 0,88)

Tumor removal

• Hepatectomy and local resection:

– Portal and liver anatomic variations

– Resected volumes according to tumor localization

Feasibility ?

Need for pre-op.

PV embolization ?

Tumor removal

• RF or microwave ablation

– Adjacent critical structures: veins, bile ducts

Access route

Type of needle

(length, diameter, …)

Portal vein embolization • Percutaneous catheterization

– Venous anatomy

Tumor embolization • Yttrium radio-embolization

– Arterial anatomy

Preoperative treatments

• Response to chemotherapy

– CT is the method of choice for oncologists : easy to read, reproducible, well established criteriae (RECIST)

Response to treatment

• Morphologic methods

– tumor size: CT RECIST

• Morphologic methods

– tumor necrosis: CT m-RECIST, Choi, EASL

• Functional methods

– tumor perfusion: CT, MR, CEUS CTP parameters

– tumor cellularity: MR diffusion ADC

– tumor activity: PET SUV

Tumor size : RECIST 1.1

• Apparently simple

– 1 question: progressive disease ? decision to change for an other treatment

– 1 major information:

• Measurement of max. 5 target lesions (2 per organ): tumors and lymphadenopathies, 1 diameter only

• % of variation the sum of diameters

– 1 algorithm

PD ? (T & NT)

yes no

PD

SD (T)

SD

Increase ΣD target L > 20%

yes no

CR

CR ? (T & NT)

Disappearance of all lesions

Disappearance of all LN > 10 mm

yes no

PR

Decrease ΣD target L < 30% PR (T) ?

Nadir

Baseline

At least 1 criteria

All criteria

The single criteria

New lesion of adenopathy

Unequivocal progression of non target lesions

Tumor size: RECIST 1.1

Tumor size : RECIST 1.1

Baseline m3

m6 m9

ΣD = 90,9 ΣD = 46,7

ΣD = 49,3 ΣD = 58,4

Δ% BL: -49%

Δ% BL: -46% Δ% BL: -36%

PR

PR PR

Δ% N-1: -49%

Δ% N-1: 6% Δ% N-1: 18%

PR

SD SD

Δ% nadir: 6% Δ% nadir: 25% SD PD

nadir

Time to progression 10 months

Time to progression 7 months

Tumor size : RECIST 1.1 1st evaluation

Present study

Baseline

1st evaluation 2nd evaluation

Case Y Menu

Tumor size : RECIST 1.1 • Not so simple

– Which reference studies : BL and nadir ?

– Which series into the reference studies ?

– Which image into the reference series : same lesion, longest diameter ?

• And also

– Need for registration tools in case of different slice thickness or field of view and automatic detection of target lesions slices

– Need for automatic calculation of the % of variations of the sum of diameters, and proposal of RECIST response

– Need for entering descriptive evaluation (new lesion, …)

Tumor size : RECIST 1.1

• Table of results and graphic visualization

• Not stored as a DICOM picture into the PACS but sent to a patient database related to the patient oncology file

A problem to anticipate

The missing metastase Nov 2012 Feb 2012 Mar 2012

?

A problem to anticipate

Surrogate markers (metallic clip)

Tumor necrosis • Low reliability of RECIST when the tumor

necrosis, instead of tumor volume, is a more appropriate indicator of the treatment result

GIST treated by Glivec 1 week 1 month 8 months

Tumor necrosis

• Estimation of the volume of viable tumor from: – The variation of mean density of the whole tumor

(Choi)

– The volume (surface) of enhanced tumor compared to necrosis (EALS, m-RECIST)

– The type of enhancement (Chun)

– … combined or not to variation of tumor volume

• All methods based on tumor necrosis assessment correlate better to patient survival compared to RECIST

Tumor necrosis

• Some limitations are however still observed

– How to accurately determine a volume (surface) of viable tumor into a heterogeneous tumor mass: ring or nodular enhancement ?

Patient management • Case of colon cancer recently removed

– Bilateral metastases predominant on right lobe

– Right hepatectomy appears to be feasible after portal vein embolization and assessment of chemotherapy response

– Request is: “place a marker into left lobe metastase in order to schedule a RF ablation (risk of disappearance of lesion after chemo.)”

?

Conclusion

• Take home messages

– MRI is needed for a accurate pre-therapeutic assessment as soon as liver resection or tumor ablation are considered

– Liver segments and tumor volumes calculation is now routinely available with recent softwares

– Patient management must be clearly organized as a step by step treatment planning