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ESTRO 36 2017
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we have applied a multiplex magnetic bead panel
(Luminex
®
) to explore associations between serum
proteins and treatment outcome in patients with locally
advanced rectal cancer.
Material and Methods
Serum samples from 22 rectal cancer patients were
collected at the time of diagnosis. All patients underwent
neoadjuvant long-course chemoradiotherapy (CRT),
according to current national guidelines. Surgery was
performed 6-8 weeks after completion of CRT and five
patients underwent adjuvant chemotherapy. CRT
responses were evaluated by ypTN staging and tumour
regression grade (TRG) (College of American Pathologists
system) scoring. The median follow-up time was 21
months (range 1-34). Using multiplex magnetic bead
technology (Luminex
®
, R&D systems), a manually selected
panel of 86 proteins involved in angiogenesis, hypoxia and
metastasis was applied to analyse serum samples.
Associations were explored using two-sided Student’s t-
tests, with p-values < 0.05 considered statistically
significant. The STRING (Search Tool for the Retrieval of
Interacting Genes/Proteins) database (
string-db.org)was
used to predict interaction networks. Survival differences
were assessed by the log-rank test and visualised by the
Kaplan-Meier method.
Results
Significant associations between several serum proteins
and TNM, ypTN, TRG and progression-free survival (PFS)
were detected. STRING analysis identified that a majority
of these proteins were involved in the PI3K-Akt signaling
pathway, and particularly angiopoietin-2 (ANGPT2) and
platelet-derived growth factor subunit B (PDGFB) were
associated to multiple end-points. By combining ANGPT2
and PDGFB, high levels were associated with both poor
histopathologic outcome (ypT3-4 versus ypT0-2: p=0.040;
TRG2-3 versus TRG1: p=0.015) (Table 1) and PFS (cut-off
8700 pg/ml, p-value 0.031), with all PFS events being
development of liver metastasis (Figure 1).
Table 1 ANGPT2 and PDGFB
Figure
1
Conclusion
Tumour angiogenesis is a major mechanism in sustained
tumour progression and the metastatic process. In the
current study, our main finding was that high serum levels
of the angiogenic factors ANGPT2 and PDGFB identified
patients with poor histopathologic response to
neoadjuvant CRT, who subsequently progressed rapidly to
metastatic disease. These results may point out an
escalating tumour aggressiveness paralleled by increasing
angiogenesis. The results were achieved in a small cohort
and require validation, but may represent an approach for
early selection of patients with an aggressive tumour
phenotype for intensified treatment strategies, perhaps
also with combinatory regimens targeting angiogenesis.
The results are currently being validated in an
independent patient cohort.
PO-0705 Work ability in Dutch rectal cancer patients
during the first year of treatment
A.M. Couwenberg
1
, M.P.W. Intven
1
, J.P.M. Burbach
1
, L.
Hupkens
2
, W.M.U. Van Grevenstein
3
, H.M. Verkooijen
4
1
UMC Utrecht, Radiotherapy, Utrecht, The Netherlands
2
Blik op Werk, Quality and research institute on
workability, Utrecht, The Netherlands
3
UMC Utrecht, Surgery, Utrecht, The Netherlands
4
UMC Utrecht, Imaging Division, Utrecht, The
Netherlands
Purpose or Objective
Rectal cancer treatment is associated with substantial
morbidity and decreased quality of life. The impact of
treatment on workability has hardly been studied. In this
study we evaluated workability in rectal cancer patients
during the first year of treatment.
Material and Methods
All working-aged rectal cancer patients (<67 years) within
the Dutch prospective colorectal cancer cohort referred
for radiotherapy at the UMC Utrecht between February
2013 and January 2016 were selected. Workability was
assessed with the Work Ability Index (WAI) Questionnaire
before start of treatment and at 3, 6 and 12 months. The
WAI score, ranging from 7 to 49, was calculated for
patients with paid employment at time of assessment and
who completed at least one questionnaire. Higher scores
reflect better workability. Workability was categorized in
poor (7-27), moderate (28-36), good (37-43) and excellent
(44-49). Results were stratified for treatment strategies
and compared with scores of the age-matched Dutch
reference population.
Results