Learning from every patient‘s biomarker - Stem cells, hypoxia, HPV and tumor volume in Dahanca 5
MO-0382
Abstract
Learning from every patient‘s biomarker - Stem cells, hypoxia, HPV and tumor volume in Dahanca 5
Authors: Jens Overgaard1, Brita Singers Sørensen1, Kasper Toustrup1, Pernille Lassen1, Jan Alsner1
1Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus N, Denmark
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Purpose or Objective
Background
and purpose: Tumor control after radiotherapy (RT) is based on eradication of all clonogenic
stem cells. Not all tumor cells possess the clonogenic potential, but genetic
biomarkers associated with stem cell density has been identified. These may be
linked with tumor hypoxia, a known cause of radioresistance. Both stem cells
and hypoxia are associated with tumor volume. HPV/p16 found
to influence the outcome of head and neck squamous cell carcinoma (HNSCC). We aim
to evaluate the impact of gene expression markers of tumor
stem cells, hypoxia and HPV in an attempt to identify patients with HNSCC
having benefit of RT with or without hypoxic modification with nimorazole.
Material and Methods
Patients and methods: Gene expressions for
stem cells (CMET, SLC3A2), hypoxia (15-gene profile), and HPV (p16) were
quantified from formalin-fixed, paraffin-embedded tumor biopsies of 270 HNSCC
patients randomized to receive placebo or nimorazole in conjunction with RT. (Radiother Oncol 102:122-9, 2012). Stem cell markers (CMET
and SLC3A2) were used to define a stem cell profile based on tertiles of
expression. This was combined with the expression of the hypoxic gene profile
in patients not given nimorazole, and taking the p16 expression into
consideration. Outcome was evaluated in terms of loco-regional tumor
control (LRC) and disease-specific survival (DSS).
Results
Results: Based on this, 4 levels of biomarker response
could be identified, with the following 5-year values for loco-regional failure
(LRF) and disease-free survival (DFS):
|
|
|
LRF
|
DFS
|
|
Level 0:
|
A ‘more hypoxic’ geneprofile, p16
neg, no nimorazole
|
87%
|
6%
|
|
Level 1:
|
High expression of CMET and SLC3A2:
|
73%
|
17%
|
|
Level 2:
|
Intermediate expression of CMET
and SLC3A2:
|
53%
|
25%
|
|
Level 3:
|
Low expression of CMET and SLC3A2:
|
37%
|
42%
|
|
|
|
P<0.001
|
P<0.001
|
Hypoxia was not found to be of
clinical importance in patients with less hypoxic gene profile, and/or p16 pos
tumors, or given treatment with nimorazole. A multivariate analysis confirmed
the value of the abovementioned levels 0-3 (HR: 0.62 [95%cf.l. 48-82] and significantly
identified the additional importance of increasing tumor volume; HR: 1.53 [1.14-2.07],
and HPV/p16; HR: 0.43 [0.28-0. 66].
Conclusion
Conclusion: Tumor biomarkers are of key importance
for the outcome after RT of HNSCC. Such individual biological information will
be useful to select the right patients to receive a more effective RT. Therefore,
to follow the theme of ESTRO 2022, and try to learn from every patient, in
order to improve RT, we must in return apply the learned knowledge in form of a
personalized adapted therapy to the individual future patient.