Radiological Early Response Assessment Of Modern Cancer Therapies

Radiological early response assessment of modern cancer therapies (Sedlaczek)

Research focus

Modern oncological therapies show tumor response patterns differing from conventional chemotherapies. This is particularly true, since initial pseudoprogressions (i.e. new lesions or inceased tumor size) are known to occur. Using standard radiological evaluation methods – Response evaluation criteria in solid tumors (RECIST 1.1) – these changes would lead to a termination of a potentially curative therapy. Atypical response patterns in immunotherapies (and checkpoint inhibition in particular) are now addressed by special immune-related response criteria in solid tumors (iRECIST). However, most progresses seen are real progresses, and techniques for early differentiation of the time course are needed.

Here the use of functional MR-techniques such as diffusion and perfusion imaging are evaluated.

The research group consists of an interdisciplinary team of scientists from the department of Radiology (E010) and the organ-specific clinical partners from the NCT (National center for tumor diseases).

Early response patterns seen are:

For cytostatic/cytotoxic therapies:

Here a patient with a SCLC before (left) and 24h after the start (right) of a platinium based chemotherapy showing an ADC decay up to 30%.
© dkfz.de

Due to the ultra early apoptosis occurring in the tumors an increased ADC can be observed regularly in successful cytostatic tumor treatments.

For TKI therapies:

Here a patient with a hepatic metastasis of an RCC before (left) and 10 days after the start (right) of a TKI-therapy showing an ADC increase.
© dkfz.de

Due to the early cellular necrosis occurring in the tumors a lowered ADC and a restricted perfusion can be observed regularly in successful TKI- tumor treatments.

For Immunotherapies:

A patient with SCLC treated with PD 1 AB; responses occurring in an delayed fasion.
© dkfz.de

As mentioned initially responses seed are heterogeneous both morphologically and with respect to the time. However, hypercellularities, such as expected for classical pseudoprogression, we did never observe, using DWI.

Research Projects

  • Prognostic impact of composition in patients with metastasized malignant melanoma with checkpoint-inhibitors therapy 

Contact: Sedlaczek/ Lonsdorf

Prognostic factors (except for PDL-staining) are largely missing using Checkpoint-inhibitors (CI). In patients being treated for malignant melanoma there might be a link between body composition (esp. adipose tissue) and therapy response.

  • Therapy monitoring in testicular germ cell tumors

Contact: Sedlaczek/ Schlemmer

Testicular cancer is by far the most common neoplasm among young males between the ages of 20 and 40 years and with an increasing incidence rate worldwide. Standard follow-up imaging is performed using CT-imaging. Since this implies using radiation in patients with a high probability of being cured limited MR-sequences are used to on one hand predict successful treatment outcome and on the other hand check for persistent treatment success.

Selected Publications

1.)      Y. Yin, O. Sedlaczek, et al. Tumor cell load and heterogeneity estimation from diffusion-weighted MRI calibrated with histological data: an example from lung cancer.  IEEE Transactions on Medical Imaging April 2017 early access

2.)      T. Persigehl, T.D. Poeppel, O. Sedlaczek. Radiological Response Guideline for Immunotherapies: iRECIST. Der Radiologe 11/17

3.)      O Sedlaczek et. al. Alteration of MR-DWI/ADC before and 24h after induction of chemotherapy in patients with lung cancer. Cancer Imaging. 2014; 14(Suppl 1)

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