MD PhD Kristina Lång · Schott AF et al., Breast Cancer Res Treat (2005) Measure changes in tumour size Kristina Lång, BCY4 Lugano 6/10 2018 2 Do not duplicate or distribute without

Neoadjuvant therapyChallenges for the radiologist

MD PhD Kristina Lång

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• Locally advanced breast cancer

• Non-locally-advanced breast cancer, such as small triple negative cancers

• The main aim is to reduce the tumour bulk

‣ Convert mastectomy to breast-conserving therapy

‣ Reduce the extent of axillary surgery

‣ In vivo assessment of tumour response

Neoadjuvant therapy

Garg PK, Prakash G Curr Oncol (2015)

Liedtke C, Rody A, Rev Recent Clin Trials (2017)

Indications

Schott AF et al., Breast Cancer Res Treat (2005)

Measure changes in tumour size

Kristina Lång, BCY4 Lugano 6/10 2018 2

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Preconditions for starting neoadjuvant therapy

1. Image the extent of the disease

2. Biopsy (cytology of LN+)

3. Marker

Three important steps


Before After

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• Complete response: disappearance of all target lesions

• Partial response: >30% reduction of the largest diameter

of the target lesion (sum of diameter if multiple lesions)

• Stable disease: neither PR or PD

• Progressive disease: >20% increase of the sum of the

target lesions or 5 mm increase in 1 lesion or new lesions

EA Eisenhauer et al. Eur J Cancer (2009)

Evaluating treatment responseRECIST criteria


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• Several imaging techniques available

• Mammography, breast tomosynthesis, and ultrasound

may be used if the index lesion was well defined by

those modalities in the pretreatment setting

• Ultrasound is more accurate than mammography

• Ultrasound is operator dependent

• Mammography have limited sensitivity in dense

breasts – BT may help

• Changes within the tumour can be difficult to evaluate

Evaluating treatment responseImaging techniques

Breast cancer Dutch Guideline, version 2.0

Keune JD et al., Am J Surg. (2010)

Berg WA, et al. Radiology (2004)

Bosch AM et al. Eur J Radiol (2003)


Dialani V et al., Ann of Surg. Onc. (2015)

TNBC

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• Contrast-enhanced MRI is the most sensitive breast imaging modality – irrespective of breast density

• MRI is the most accurate in determining residual disease after NAC compared to physical

examination, mammography and ultrasound

• MRI can both overestimate or underestimate residual tumor size (10–20%)

• Some studies suggest that ultrasound is at least as good as MRI in predicting tumour size post NAC

Magnetic resonance imagingImproved accuracy

Sardanelli F, et al. Eur J Cancer (2010)

Yuan Y et al, AJR (2010)

Marinovich ML, et al. Breast. (2012)

Marinovich ML, et al. J Natl Cancer Inst. (2013)

Marinovich ML, et al. Br J Cancer (2013)

Kristina Lång, BCY4 Lugano 6/10 2018

Vriens B.E.P.J. et al., Eur J Cancer (2016)

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• NAC causes various histopathological changes in

tumor cellularity, leading some tumors to different

response patterns

• Dependent on tumour type (TNBC, ER+/HER2-

more often shrinking mass)

• Response patterns measured halfway through

NAC correlate better with pCR than MRI after NAC

Magnetic resonance imagingResponse patterns

Loo CE, et al., J Clin Oncol (2011)

Goorts B et al., Breast Cancer Res Treat (2017)Concentrical shrinkage

Before Interim

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• Tumor size assessment can be challenging for certain

treatment response patterns

• Fragmentation: scattered foci cannot be measured

independently on MRI

Magnetic resonance imagingChallenges

Kim TH, et al. Comput Assist Tomogr. (2012)

Goorts B et al. Breast Cancer Res Treat (2017)


Fragmentation

Before After

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• The overall loss of vital tumor cells might not

always be reflected by a reduction in tumor

size

• Fibrous stroma might persist and even be

enhanced on MRI

Magnetic resonance imaging

Before After

Li YL et al. Eur J Radiol (2015)

Challenges


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The use of MRI in Europe

• More frequently performed in academic centres

(92.1% compared to 78.3% in community hospitals

and 70% in private hospitals, p=0.006).

• The difference between academic and non-academic

centres was particularly evident for the evaluation of

early response

• MRI is expensive, time-consuming and might not

always be available

For NAC evaluation

Clauser P, et al. Eur Radiol (2017)


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Guidelines

• EUSOMA working group:

‣ Pretreatment breast MRI should be performed in patients with large potentially operable breast cancer

before the first course of NAC, at the condition that performing MRI does not significantly postpone NAC

initiation.

• ESMO clinical guidelines:

‣ Breast MRI is the most accurate modality for assessing the extent of residual disease following neoadjuvant

treatment.

• Breast cancer Dutch guideline:

‣ MRI as additional imaging technique is recommended to accurately record the tumour size before and after

neoadjuvant chemotherapy (unless it can be clearly determined using mammography and ultrasound)

Sardanelli F et al., EJC (2010)Fowler et al., Radiology (2017)Senkus E et al., Annals of Oncology (2015) Breast cancer Dutch Guideline, version 2.0


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An evolving field

• Current imaging methods are not perfect

• New imaging approaches:

‣ Contrast-enhanced spectral mammography

‣ Shear wave elastography

‣ And many others…


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Contrast enhanced spectral mammography (CESM)

• New imaging technique (FDA 2011)

• Iodinated contrast agent

• Dual energy exposure

• High sensitivity, low specificity

• Cost-effective alternative to MRI?Low energy High energy Recombined

image

Tagliafico et al. Breast (2016)


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CESM

Iotti V et al., Breast cancer research (2017)

• Small prospective study (n=46) comparing MRI and CESM

before, interim and after NAC

• In the assessment of CR, CESM had higher sensitivity and

specificity (100% and 84%) compared to MRI (87% and

60%)

• Both methods tend to underestimate the extent of residual

disease

• Conclusion: ”CESM seems at least as reliable as MRI in

assessing the response to NAC, and may be an alternative

if MRI is contraindicated or its availability is limited.”


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Shear wave elastography

• Ultrasound method that measures tissue stiffness

• A significant increase in specificity

Evans A et al., Ultraschall in Med (2018)

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• Small prospective study (n=64) evaluating baseline and

interim imaging with US, SWE and MRI for prediction of pCR

• SWE outperformed US and MRI

• Changes in SWE stiffness are strongly associated with pCR

Berg WE et al. Radiology (2012)

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MICRA trial

• PCR rates after NAC are increasing – de-escalation of local treatment

• Imaging methods are not sufficiently accurate to identify pCR to replace surgery

• The MICRA trial investigates the value of biopsies in identifying pCR

• Breast surgery could be omitted in patients with pCR

MICRA study; TrialRegister.nl, number NTR6120

Minimally Invasive Complete Response Assessment

van der Noordaa M.E.M. et al., The Breast (2018)

To be continued…


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Neoadjuvant therapy from a radiologist perspective

• Appropriate initial imaging examinations to determine

disease extent include mammography and ultrasound

(and if available breast tomosynthesis)

• If tumour extent cannot be reliably be determined

additional MRI is needed

• MRI is the most accurate imaging method to assess

NAC response

• No imaging method today is 100% accurate to

determine pCR

• MRI can both over- and underestimate residual

disease

• New imaging methods are under evaluation

Take home message

Challenges


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Thank you for your attention

[email protected]

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Documents

MD PhD Kristina Lång · Schott AF et al., Breast Cancer Res Treat (2005) Measure changes in tumour size Kristina Lång, BCY4 Lugano 6/10 2018 2 Do not duplicate or distribute without