Adaptive Treatment, Locally Advanced Rectal Carcinoma, Neoadjuvant Treatment, Radiotherapy
Conditions
Keywords
total neoadjuvant therapy (TNT), T2* MRI, circulating tumor cells, tumor infiltrating lymphocytes, liquid biopsy, DWI, rectal cancer, organ preservation
Brief summary
This pilot study aims to trial multimodal early response assessment to enable therapy adaptions in the context of non-operative therapy strategies of locally advanced rectal cancer (LARC) for development of a non-invasive response prediction model.
Detailed description
Patients with LARC, receiving neoadjuvant chemoradiotherapy (CRT) are followed by at least 4 multiparametric MRI-scans (diffusion weighted imaging and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyse circulating tumour cells (CTCs). A standard pelvis radiotherapy (RT, 5040 cGy) will be performed in combination with a 5-Fluorouracil / Oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional histologic markers, such as tumour-infiltrating lymphocytes (TILs) or PD-L1 status will be analysed before and after CRT. Resection is standard after completion of preoperative treatment. In case of complete regression and patient's request, a non-operative management ("watch and wait") is offered alternatively. The primary endpoint is response, defined by tumor regression grading, secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TILs.
Interventions
DIAGNOSTIC_TESTBlood sample
longitudinal blood samples for CTC monitoring
DEVICEMRI scan
longitudinal MRI scans (non-contrast enhanced)
Sponsors
Jena University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* locally advanced rectal cancer (LARC): UICC Stage II/III * no severe cardiac or lung disease * no severe hepatic disorders (liver enzymes \<2.5 NR) or restrictions of renal function (GFR \> 30ml/min) * no severe cytopenia (Neutrocytes \>= 3 Gpt/l; Thrombocytes \>= 100 Gpt/l; Hemoglobin \>6mmol/l) * no homozygotic DPD deficiency * no other neoplasms requiring therapy * no earlier radiotherapy of the pelvis or earlier chemotherapy * no contraindications for MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor regression grading (TRG) | after completion of neoadjuvant treatment (up to 10 months) | Histological response assessment by TRG (Werner / Hoefler et al.); Complete response is defined as TRG 1a; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI | up to 10 months, until resection | longitudinal changes in multiparametric MRI sequences (diffusion weighted and hypoxia sensitive) |
| Circulating Tumor Cells (CTC) | 5 years | longitudinal changes in CTCs |
| Tumor Infiltrating Lymphocytes (TIL) | up to 10 months, until resection | longitudinal changes in TILs |
| PFS | 5 years | progression free survival |
| OS | 5 years | overall survival |
| Surrogate marker: Interleukin 6 (IL-6) | 5 years | surrogates of tumor and inflammation from routine blood draws \[ng/l\] |
| Surrogate marker: Carcinoembryonic Antigen (CEA) | 5 years | surrogates of tumor and inflammation from routine blood draws, \[mg/l\] |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATORAndrea Wittig-Sauerwein, MD
Department for Radiotherapy and Radiooncology, Jena University Hospital
Outcome results
None listed