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Vienna, Austria

ESTRO 2023

Session Item

Monday
May 15
09:00 - 10:00
Stolz 1
Head & neck
Francesca De Felice, Italy;
Nadine Vatterodt, Denmark
Mini-Oral
Clinical
09:00 - 10:00
Tumor volume and cancer stem cells as prognostic markers for loco-regional control in HNSCC
Morten Horsholt Kristensen, Denmark
MO-0715

Abstract

Tumor volume and cancer stem cells as prognostic markers for loco-regional control in HNSCC
Authors:

Morten Horsholt Kristensen1, Jan Alsner1, Brita Singers Sørensen1,2, Christian Rønn Hansen2,3,4, Ruta Zukauskaite5, Eva Samsøe6, Christian Maare7, Jørgen Johansen5, Hanne Primdahl8, Åse Bratland9, Claus Andrup Kristensen10, Maria Andersen11, Jacob Kinggaard Lilja-Fischer1, Trine Tramm12, Jens Overgaard1, Jesper Grau Eriksen1

1Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark; 2Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus, Denmark; 3Odense University Hospital, Laboratory of Radiation Physics, Odense, Denmark; 4University of Southern Denmark, Department of Clinical Research, Odense, Denmark; 5Odense University Hospital, Department of Oncology, Odense, Denmark; 6Zealand University Hospital, Department of Oncology, Næstved, Denmark; 7Herlev Hospital, Department of Oncology, Herlev, Denmark; 8Aarhus University Hospital, Department of Oncology, Aarhus, Denmark; 9Oslo University Hospital, Department of Oncology, Oslo, Norway; 10Rigshospitalet, Department of Oncology, Copenhagen, Denmark; 11Aalborg University Hospital, Department of Oncology, Aalborg, Denmark; 12Aarhus University Hospital, Department of Pathology, Aarhus, Denmark

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Purpose or Objective

Radioresistance is assumed to be the main reason for failure after primary curative (chemo-)radiotherapy ((C-)RT) for HNSCC. Characterization of radioresistant tumors is debated, but has been suggested to be linked to the absolute number of cancer stem cells (CSC). We aimed to identify if putative CSC markers and tumor volume could identify patients (pts) with different outcome following primary (C-)RT.

Material and Methods

The DAHANCA 19 cohort from 2007-12 was included. Treatment was primary curative IMRT-based (C-)RT (66-68Gy/33-34fx 6 fx/wk (+/- cisplatin 40mg/m2 weekly)) and nimorazole. Primary (GTV-T) and nodal (GTV-N) volume was extracted from planning-CTs. RNA qPCR from formalin-fixed paraffin embedded (FFPE) tumor tissue was used to analyse gene expression of putative CSC markers (SLC3A2 and MET). p16-status was determined by immunohistochemistry (cut-off: 70%).

The absolute number of CSC was estimated as the sum of the products of tumor volume (V) and expression (Exp) of CSCs:

CSC(total) = V(tumor) × Exp(SLC3A2) + V(tumor) × Exp(MET)

Analyses were conducted separately on groups of pts with p16-positive oropharyngeal (OPSCCp16+) and non-HPV-driven tumors.

Variables were categorized group-vice in tertiles and evaluated by Kaplan-Meier-method and Cox regression analyses. Endpoints were 3-year T-site failure in analyses where primary tumor volume (GTV-T) was a factor, N-site failure with nodal volume (GTV-N) and loco-regional failure (LRF) with total tumor volume (GTV-Tot).

Results

Of 600 pts, 545 pts were included: OPSCCp16+ (n=282) and non-HPV-driven (n=263 (OPSCCp16- (n=100); oral cavity (n=20); hypopharynx (n=65); larynx (n=78))). Pts were excluded in cases of insufficient tumor tissue in the FFPE block (n=35) and due to missing volume data (n=20).

For non-HPV-driven tumors, large total tumor volume (GTVTot) was a poor prognostic factor for LRF (Figure 1). The hazard ratio (HR) for LRF for the large volume-group was 3.2 (95 %CI: 1.7-5.7) compared to small volume. Number of CSC increased the ability to distinguish a group with lower risk of LRF, with HR=2.5 (1.2-4.9) for intermediate vs. low CSC and HR=2.7 (1.4-5.4) for high vs. low CSC number.

Total volume was not prognostic for pts with OPSCCp16+ (Figure 2). The number of CSCs was able to identify groups with different risks of LRF. Pts with high number of CSCs had a higher risk (HR=4.4 (1.6-11.7)) of LRF compared to low CSC.

For both OPSCCp16+ and non-HPV-driven tumors, a similar pattern was reflected in the risk of T- and N-site failure. Higher risk of failure for non-HPV-driven tumor was seen for pts with larger volume as well as with higher number of CSC. For OPSCCp16+ tumors, the absolute CSC number distinguished groups with higher and lower risk of failure (HR=3.0 (1.2-7.7) for N-site failure for high vs low CSC number).



Conclusion

Tumor volume was prognostic for the non-HPV-driven tumors only. In contrast to volume, the level of CSC was prognostic in OPSCCp16+, which may benefit in selection of pts for individualized treatment.