Session 16: Tumors
15. November
12:45 - 13:45
Lokale: Sal B
Chair: Christina Holm & Thomas Baad-Hansen
128. Effect on Survival after Implementation of Danish Cancer Patient Pathways in Deep-Seated High-Grade Soft Tissue Sarcomas in the Extremities and Trunk Wall: A Retrospective Observational Study
Andrea Thorn1, Kristoffer Seem1, Michala Skovlund Sørensen1, Ninna A. Pedersen2, Thomas Baad-Hansen3, Michael Mørk Petersen1
1. Rigshospitalet – University of Copenhagen, Department of Orthopaedic Surgery
2. Aarhus Universitetshospital, Department of Oncology
3. Aarhus Universitetshospital, Department of Orthopaedic Surgery
Background: Soft tissue sarcomas (STS) are rare cancers
originating in the body’s connective tissues,
presenting diagnostic challenges due to diverse and
unspecific symptoms. Efforts to improve diagnostic
processes, such as the implementation of Danish
Cancer Patient Pathways (CPP) in 2009, have
shown promise in reducing sarcoma size and
diagnostic time intervals. However, the direct impact
of CPPs on sarcoma patient survival remains
uncertain.
Aim: We aim to assess changes in overall survival
between national cohorts of STS high-grade patients
pre- and post-CPP implementation.
Materials and Methods: We included all patients above the age of 18
years in Denmark with biopsy confirmed
diagnosis of high malignant STS (Trojani grade
2+3). Only patients with MR conform deep-
seated sarcoma in the extremities or trunk wall,
diagnoses from January 1, 2000, to December
31, 2016, were included. Patients diagnosed in
the year 2009 were excluded due to different
startup points with the implementation of CPP
between the two sarcoma centers in Denmark,
resulting in a pre-and post-CPP implementation
cohort. Patients were followed until death or end
of study (01-01-2024)Statistics: Kaplan Meir
Survival analysis, log-rank test, and Mann–
Whitney test.
Results: A total of 615 adult patients diagnosed with localized
deep-seated high malignant STS in the extremities
and trunk wall, were identified (Before 2009 (BF): n=
314, After 2009 (A): n=301). 306 patients died during
the follow-up (BF: n= 138, A: n= 168). The 5-year
overall survival rates were 44% (CI-95: 39-49%) and
59 % (CI-95: 50-61%) for respectively BF and A (p<
0.001). Median tumor size BF: 10 cm (0.5-30) and A:
9.5 cm (1-40), (p=0.4).
Interpretation / Conclusion: A statistically significant increased survival was
observed after the implementation of CPP in
patients with high malignant deep-seated STS.
Despite prior studies indicating reduced tumor size
with CPP, we have not been able to verify this
finding.
129. Elevated cobalt levels in metal-on-polyethylene knee megaprostheses: a prospective 1-year cohort study of 56 patients with hip and knee megaprostheses
Sarah Stammose Freund1, Andrea Pohly Jeppesen Thorn 2, Ajay Puri 3, Michael Mørk Petersen2, Thomas Baad-Hansen 1
1 Department of Orthopedic Oncology, Aarhus University Hospital, Denmark; 2
Department of Orthopedic Surgery, Rigshospitalet - University of Copenhagen,
Denmark; 3 Surgical Oncology, Orthopedic Oncology, Tata Memorial Centre,
HBNI, Mumbai.
Background: Concerns have emerged regarding elevated
levels of cobalt and chromium in patients with
metal-on-metal megaprostheses, however few
studies on metal-on-polyethylene
megaprostheses exists.
Aim: This prospective study aims to identify systemic
cobalt and chromium levels in metal-on-
polyethylene knee and hip megaprostheses and
their associations with other factors.
Materials and Methods: 56 patients underwent knee or hip
megaprosthesis surgery at 2 sarcoma centers.
Serum cobalt and chromium levels were
measured preoperatively and thrice within the
first year using Inductively Coupled Plasma
Mass Spectrometry.
Results: Following knee megaprosthesis surgery, there
was a significant increase in serum cobalt levels
(1.4 ppb; 95% CI 0.0–3.3) at 1-year compared
to preoperative levels. Conversely, chromium
levels in the same group showed no significant
change after 1 year compared to preoperative
levels (0.05 ppb; CI 0.0–0.8). Additionally, none
of the other megaprostheses groups showed
elevated cobalt or chromium over time.
Associations were observed between younger
age, higher eGFR, and elevated cobalt levels.
However, no significant correlations were found
between ion levels and resection length or the
number of modular connections.
Interpretation / Conclusion: Our findings demonstrate elevated serum ion
levels in metal-on-polyethylene knee
megaprostheses, contrasting with metal-on-
polyethylene hip megaprostheses. Furthermore,
positive correlations between cobalt and
chromium levels, as well as cobalt and eGFR,
were noted, along with a negative correlation
between cobalt and age, indicating that younger
patients with higher activity levels and better
eGFR tend to exhibit higher metal ion levels.
Notably, contrary to previous suggestions by
other authors, we did not observe any
association between metal ion levels and
resection length. This study highlights the
importance of monitoring systemic cobalt and
chromium levels in patients with knee
megaprostheses.
130. Effect of repeated bolus and continuous doxorubicin administration on bone and soft tissue concentrations – a randomized tumour-free porcine model
Andrea René Jørgensen 1,2, Mats Bue1,2,3 , Pelle Hanberg 1,2, Harlev Christina1,2, Krogsgaard Petersen Elisabeth 1,2, Rasmussen Hans Christian 1,2, Hansen Jakob 4, Baad-Hansen Thomas2,3, Safwat Akmal 2,5, Stilling Maiken 1,2,3
1. Aarhus Microdialysis Research Group, Orthopaedic Research Unit,
Aarhus University Hospital, Aarhus N, Denmark;
2. Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark;
3. Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus
N, Denmark;
4. Department of Forensic Medicine, Aarhus University Hospital, Aarhus N,
Denmark;
5. Department of Oncology, Aarhus University Hospital, Aarhus N,
Denmark;
Background: Doxorubicin is a central part of many
chemotherapeutic regimens, here amongst
osteosarcoma. Despite being applied
clinically for decades, very little is known
about local tissue concentrations of
doxorubicin as pharmacokinetic knowledge
regarding dosing regimens are almost
solely based on plasma concentrations.
Aim: The aim of this study was to evaluate
plasma and bone- and soft-tissue
concentrations of doxorubicin following two
administrations of either bolus or
continuous infusion administered at a three-
week interval.
Materials and Methods: Eighteen female pigs were included in
the study and randomized into two
groups of nine. Based on mean body
weight, animals received a doxorubicin
dosage of 132 mg (2 mg/kg) on day 1
and a dosage of 150 mg on day 22, as
either bolus or continuous infusion. From
day 1 to 10, doxorubicin concentrations,
as well as kidney and liver function, were
monitored with plasma samples (total
concentrations). On day 22, doxorubicin
was measured in plasma samples (total
concentration) and microdialysates
(unbound concentrations) from
subcutaneous tissue, muscle, synovial
fluid of the knee joint, cancellous bone,
and intravenously.
Results: On day 22, the pharmacokinetic profiles
were comparable between the two groups
except for plasma AUC0-12h, which was
higher after continuous infusion, and
intravenous Cmax, which was higher after
bolus infusion. Bone- and soft tissue
concentrations were below 0.10 ug/mL.
With the exception of mean plasma (total)
concentration after 6 h on day 1 and 22 in
the continuous group which was higher
after the first administration (p=0.037), no
differences in plasma concentrations were
found between the two administrations.
Interpretation / Conclusion: Low mean tissue doxorubicin
concentrations and similar pharmacokinetic
profiles were found between the bolus and
continuous infusion groups. Thus, similar
anti-neoplastic efficacy is to be expected
with both administration types.
131. Injectable sustained local release doxorubicin depot technology – a promising adjuvant to systemic treatment?
Andrea René Jørgensen 1,2, Anders Elias Hansen 3, Jonas Rosager Henriksen 3, Maiken Stilling1,2,4, Hans Christian Rasmussen1,2, Johanne Gade Lilleøre1,2, Magnus Andreas Hvistendahl1,2, Josefine Slater1,2, Elizabeth Serrano-Chávez3, Jakob Hansen5, Mats Bue1,2,4
1. Aarhus Denmark Microdialysis Research (ADMIRE), Orthopaedic
Research Unit, Aarhus University Hospital, Aarhus N, Denmark;
2. Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark;
3. Department of Health Technology, Section for Cell and Drug
Technologies, Technical University of Denmark, Lyngby, Denmark;
4. Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus
N, Denmark;
5. Department of Forensic Medicine, Aarhus University Hospital, Aarhus N,
Denmark.
Background: The local application of drug depot
technologies releasing chemotherapeutics
in cancerous tissues presents an interesting
strategy for enhancing treatment outcome
by increasing and sustaining high local
chemotherapeutic concentrations.
Aim: This study aimed to assess the feasibility,
delivery capacity, and therapeutic efficacy of
a doxorubicin-loaded carbohydrate-ester-
based (CarboCell) depot technology as a
localized drug delivery system.
Materials and Methods: CarboCell was investigated in three
experimental setups: A) Release kinetics
were evaluated in mice (non-tumour model)
24 h and 48 h after a subcutaneous
injection of depot. B) Efficacy in terms of
tumour growth control and survival was
evaluated in mice carrying large syngeneic
CT 26 colorectal cancer. A volume of 50 µl
CarboCell containing 1 mg/mL or 4 mg/mL
doxorubicin was injected in the tumours
twice at 5 days intervals. C) Local and
distant release of doxorubicin CarboCell 2
mg/mL (2 mL or 4 mL) injected into tibial
metaphysis was evaluated with
microdialysis in nine tissue compartments in
ten female pigs.
Results: A) Subcutaneous CarboCell depots
displayed a continuous release of
doxorubicin with 36±13% (mean±SEM) and
48±20% of the loaded dose being released
at 24 h and 48 h time points. B) Intratumoral
injection demonstrated robust tumour
growth control and significantly prolonged
median survival time compared to the
control group. C) In the porcine model,
irrespective of volume injected (2 or 4 ml),
doxorubicin could be measured at least 10
mm from the application site in cancellous
bone indicating a good metaphyseal
distribution. The systemic spill-over was
minimal, and only measurable in three out
of ten animals.
Interpretation / Conclusion: Doxorubicin-loaded CarboCell proved easily
administrable with maintained antitumoural
activity and was able to provide much
higher local doxorubicin concentrations
when injected in metaphyseal bone
compared traditional systemic
administration. Importantly, minimal
systemic spill-over was observed,
supporting further exploration of efficacy
and tolerability in combination therapies.
132. Physical function following megaprosthesis surgery in the lower limb - a prospective cohort study of 38 patients.
Sarah Stammose Freund1, Michael Melchior Bendtsen1, Bjarne Hauge Hansen1, Henning Andersen2, Thomas Baad-Hansen1
1 Department of Orthopedic Oncology, Aarhus University Hospital, Denmark; 2
Department of Neurology, Aarhus University Hospital, Denmark
Background: Limited knowledge exists on early outcomes
post-megaprosthesis surgery. Yet, in counseling
of patients understanding these outcomes is
crucial.
Aim: This prospective study investigates physical
function outcomes in lower limb megaprosthesis
surgery patients, employing both objective and
subjective measures, while also identifying their
associations.
Materials and Methods: 38 patients underwent treatment with a proximal
femur, distal femur, or proximal tibia
megaprosthesis. Muscle strength tests, range of
motion evaluations, the Timed Up and Go test,
and the Musculoskeletal Tumor Society score
were conducted at 4, 8, and 12-18 months post-
surgery. Repeated measurements analysis was
performed along with a comparison between
treated limb, untreated limb, and predictive
values.
Results: : Bilateral muscle strength reduction, especially
in regions subjected to surgical intervention,
was observed, with the proximal tibia group
showing the most pronounced deficits. None of
the groups exhibited statistically significant
changes in strength over time. All groups had
decreased joint flexion in the treated limb
compared to the untreated limb 12-18 months
post-surgery. Timed Up and Go performance
improved in all groups but remained below
average compared to reference values. An
association was observed between a lower
Timed Up and Go Test and higher
Musculoskeletal Tumor Society scores, with the
latter being lowest in the proximal tibia group.
Interpretation / Conclusion: The study provides data from comprehensive
testing the first year following megaprosthesis
surgeries providing knowledge in order to inform
and guide patients. Markedly reduced strength
in both treated and untreated limbs compared to
predicted normal values was observed. The
significant deficit in walking capabilities showed
clear association to patients' reported outcomes.
133. Survival and local recurrence of patients with leiomyosarcoma in the extremities and trunk wall in Denmark from 2000 to 2016.
Ingrid Frederikke Gottlieb(1), Andrea Pohly Jeppesen Thorn (1), Thomas Baad-Hansen (2), Ninna Aggerholm-Pedersen(3), Michael Mørk Petersen(1),
1. Department of Orthopedic Surgery, Rigshospitalet, Copenhagen;
2. Department of Orthopedic Oncology, Aarhus University Hospital;
3. Department of Oncology, Aarhus University Hospital.
Background: Leiomyosarcomas are rare malignant tumors
originating from mesenchymal cells, and these
tumors can develop anywhere in the body from
blood vessels or smooth muscle cells. The overall 5-
year survival probability of patients with
leiomyosarcomas in previously published larger
European studies is around 60%.
Aim: In this study, we aimed to determine the survival and
risk of local recurrence among patients treated for
leiomyosarcomas in Denmark between 2000 and
2016.
Materials and Methods: The study involved a thorough analysis of patient
data obtained through national databases. A total
of 309 patients were initially registered with
leiomyosarcoma. The patients were then
screened based on the following exclusion
criteria: treatment before the year 2000,
age below 18 years, and a tumor localization
other than either the extremities or trunk wall.
The collected data were categorized and
analyzed statistically using Kaplan-Meier
estimation with calculation of the probability of 5-
year survival with 95% confidence interval (CI-
95).
Results: 290 patients (female/male=115/175, median
age(range) = 63(18-96) years) diagnosed with
leiomyosarcoma were included in the study, and
the 5-year overall survival probability was 67%
(CI-95: 62-73%). 5-year survival was 81% (CI-
95: 71-90%) for tumors located in the upper
extremities, 61% (CI-95: 53-69%) for lower
extremities, and 67% (CI-95: 56-79%) for tumors
in the trunk wall.
Stratification by tumor grade revealed 5-year
survival probabilities of 88% (CI-95: 81-96%) for
grade 1, 81% for grade 2 (CI-95: 73-89%), and
46% (CI-95: 38-55%) for grade 3. 5-year survival
was 80% (CI-95: 74-86%) and 43% (CI-95: 34-
52%) for tumor size below 5 cm and above 5 cm.
A total of 52/290 (18%) of the patients
experienced a local recurrence and their 5-year
survival was 50% (CI-95: 36-64%) compared to
71% (CI-95: 65-76%) for those without local
recurrence.
Interpretation / Conclusion: Our findings suggest that Danish patients exhibit
survival probabilities consistent with the European
standard. This indicates that the treatment of Danish
patients with leiomyosarcoma is satisfactory.
134. Vascularized Fibular Grafting for Reconstruction After Tumor Resection in Denmark from 2009 to 2023
Christian L. Nielsen1., Daniel T. H. Dybdal2., Peter Vester-Glowinski3., Lisa Lyngsie Hjalgrim2., Henrik Hasle4., Birgitte J. Kiil5., Michael M. Bendtsen1., Michael M. Petersen6., Thomas Baad-Hansen1.
1. Department of Orthopedic Surgery, Aarhus University Hospital, Denmark
2. Department of Paediatrics and Adolescent Medicine, University Hospital
Copenhagen, Denmark
3. Department of Plastic Surgery and Burns Treatment, University Hospital
Copenhagen, Denmark
4. Department of Paediatrics and Adolescent Medicine, Aarhus University
Hospital, Denmark
5. Department of Plastic and Breast Surgery, Aarhus University Hospital,
Denmark.
6. Department of Orthopedic Surgery, University Hospital Copenhagen, Denmark
Background: Vascularized fibula grafting following tumor
resection is an important component in limb
salvage surgery.
Aim: The purpose of this study was to determine both
surgical and oncological outcomes of patients
treated in Denmark between 2009 and 2023.
Materials and Methods: We describe a retrospective review of 27
consecutively treated patients who
underwent surgery between the 1st of
January 2009 and the 1st of November 2023
at Aarhus and Copenhagen University
Hospitals. Patients were identified from the
national Danish Sarcoma Database. There
were 12 cases of osteosarcoma, 13 cases of
Ewing’s sarcoma and 2 cases of Giant cell
tumor. Mean age at the time of surgery was
15.1 years (range: 2.4-38.9). Mean follow-up
was 74.8 months (range: 12-138). Patients
were analyzed overall and stratified on basis
of tumor location in an upper and a lower
extremity group.
Results: During the follow-up period, 18 patients
attained graft union (66.7 %) with a mean
time to union of 13.9 months (range: 7-28.5).
6 patients developed nonunion (22.2 %) and
20 patients (74.1 %) had to undergo one or
more reoperations in relation to the primary
surgery. Patients in the upper extremity
group were more likely to attain graft union
(91.7 % vs. 46.7 %, RR=5.5, 95 % CI=1.3-
31.5, p=0.02) and less likely to undergo
multiple reoperations (16.7 % vs 60 %,
RR=0.3, 95 % CI:0.1-0.9, p=0.047)
compared to patients in the lower extremity
group. 6 patients died during follow-up. Five-
year overall survival was 81.2 % (95 % CI:
60.5-91.7). 8 patients (29.6 %) experienced
relapse with distant metastases. Among
these patients, 5 also developed local
recurrence (18.5 %). Mean time to
metastasis was 10.3 months (range: 1-18)
while mean time to local recurrence was
13.2 months (range: 7-17).
Interpretation / Conclusion: Biological reconstruction with VFG after tumor
resection remains a reasonable option, despite
the low rate of graft union and the need for
multiple reoperations, particularly in lower
extremity cases.