ESTRO 36 Abstract Book

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S527 ESTRO 36
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Poster: Radiobiology track: Normal tissue biology of the
heart
PO-0952 Integral heart dose and lymphocytopaenia in
lung cancer patients treated with radical radiotherapy
N. Joseph1, A. McWilliam2, K. Haslett 2, J. Kennedy2, C.
Faivre-Finn2, A. Choudhury2
1 General Hospital Polonnaruwa, Clinical Oncology,
Polonnaruwa, Sri Lanka
2 The Christie NHS Foundation Trust, Clinical Oncology,
Manchester, United Kingdom
Purpose or Objective
Optimal radiation dose delivery in lung cancer patients is
limited by the risk of toxicity to adjacent organs especially
the heart, lung and spinal cord. Post-treatment
lymphocytopaenia is a recognised complication in patients
undergoing thoracic radiotherapy and if severe, can lead
to opportunistic infections. We hypothesised that a higher
integral heart dose is associated with post-treatment
lymphocytopaenia in patients with small cell lung cancer
(SCLC) and non-small cell lung cancer (NSCLC) treated
with radical radiotherapy.
Material and Methods
138 patients (103 NSCLC and 32 SCLC) treated with radical
radiotherapy were included in this study. Concurrent
chemotherapy was administered in 85/135 patients.
Prescribed dose to planning target volume ranged from
41.4 to 72 Gy with a median of 66 Gy. Lymphocyte counts
prior to treatment and up to 100 days post-treatment were
obtained. The integral heart dose was derived by using the
product of mean dose and volume. A linear mixed effects
model, incorporating the following variables: integral
heart dose, integral heart dose per fraction, baseline
lymphocyte count, time from start of treatment and use
of concurrent chemotherapy was used to analyse the
effect on post-treatment lymphocyte counts
Results
The median integral heart dose in the cohort was 14.5
Litres-Gy (range 4-35.6). Integral heart dose (p=0.03) and
time from start of therapy (p < 0.001) were negatively
correlated with post-treatment lymphocyte counts while
integral heart dose per fraction (p=0.05) and baseline
lymphocyte count (p<0.001) were positively correlated.
Use of concurrent chemotherapy was not statistically
significant in the model.
Conclusion
Total integral heart dose predicts a lower post-treatment
lymphocyte count in lung cancer patients treated with
radical radiotherapy. The positive correlation with higher
integral heart dose per fraction suggests that fractionation
has an adverse effect on post-radiotherapy lymphocyte
counts.
Poster: Radiobiology track: Radiobiology of the
intestinal track
PO-0953 Proteome profiles in PDAC patients with local
recurrence after postoperative radiochemotherapy
L. Bolm1, V. Oria2, L. Kaesmann 3, P. Bronsert4, U.F.
Wellner5, O. Schilling 6, D. Rades 3
1 University of Luebeck, Department of Radiation
Oncology- Department of Visceral Surgery, Lübeck,
Germany
2 University of Freiburg, Department of Molecular
Medicine and Cell Research, Freiburg, Germany
3 University of Luebeck, Department of Radiation
Oncology, Luebeck, Germany
4 German Cancer Consortium DKTK and German Cancer
Research Center DKFZ, Department of Pathology,
Heidelberg, Germany
5University of Luebeck, Department of Visceral Surgery,
Luebeck, Germany
6German Cancer Consortium DKTK and German Cancer
Research Center DKFZ, Institute of Molecular Medicine
and Cell Research- Freiburg, Heidelberg, Germany
Purpose or Objective
Complete surgical resection remains the only curative
option in patients with pancreatic ductal adenocarcinoma
(PDAC). Microscopically incomplete resection (R1) is often
associated with early local recurrence (LR) and, therefore,
represents a negative prognostic factor. The aim of this
study was to analyze the total PDAC proteome of patients
who received radiochemotherapy (RCT) following
incomplete resection in order to identify proteins
associated with post-RCT LR.
Material and Methods
Thee patients with early LR (median 6 months after
resection, range 5 to 10 months) and three patients with
late LR (median 18 months after resection, range 13 to 27
months) were identified from our clinical database.
Formalin fixed paraffin-embedded tissue obtained from
surgical PDAC specimens was used for proteome analysis.
After micro-dissection, tissue was de-paraffinized and
rehydrated, followed by protein extraction and trypsin
digestion. The samples were analyzed by tandem mass
spectrometry. To identify significantly up- or down-
regulated proteins, linear models for microarray data
(LIMMA) were applied; the p-value was set to 0.01.
Results
Patients received a median RT total dose of 50.4Gy and
concurrent chemotherapy with two courses of 5-FU.
Overall survival was reduced in patients with early LR as
compared to patients with late LR (7 vs. 30 months,
p=0.0001). A total of 1,878 proteins were quantified in
both cohorts with 1,656 proteins quantified in the early LR
group and 1,769 quantified in the late LR group. LIMMA
method identified 18 proteins significantly up- or down-
regulated. 7 proteins were up-regulated in the early LR
group such as MAOA, ALDH1A1, creatine kinase B and
mucin-5AC being involved in tumorigenesis. 11 proteins
were up-regulated in the late LR group including fascin,
integrin beta-4, histidine rich glycoprotein and CDC42.
Further analysis demonstrated the early LR group to
exhibit an exocrine-like phenotype including expression of
pancreatic proteins absent in the late LR group. 13
exocrine-related proteins were identified such as
carboxypeptidase B and chymotrypsin-C.
Conclusion
Analyzing proteomic data of PDAC patients undergoing
post-operative RCT after R1-resection, proteomic
expression profiles associated with early vs. late post-RCT
LR were identified. These proteomic biomarkers may
serve to stratify patients according to prognosis in future
trials and to assess a potential benefit of post-operative
RCT.
PO-0954 A model to study long-term impact of
radiation towards the colorectal area
F. Sjöberg1, D. Malipatlolla1, G. Steineck 1, C. Bull1
1The Division of Clinical Cancer Epidemiology,
Department of Oncology- University of Gothenburg,
Gothenburg, Sweden
Purpose or Objective
A deeper understanding of the radiophysiology following
radiotherapy is imperative. With a few exceptions, rodent
models of high-dose gastrointestinal radiation injury
typically cause lethality within 5-8 days, limiting the
possibility to study the progression of injury over time. We
have developed a model that allows for delivering
radiation in fractions at high doses, while maintaining
excellent survival.