Session 6: Tumor
Torsdag den 23. oktober
09:30 – 10:30
Lokale: Helsinki/Oslo
Chairmen: Werner Herbert Hettwer / Jørgen Peter Holmberg
Jørgensen
53. Excess mortality in soft tissue sarcoma patients: a Danish population-based study
Katja Maretty-Nielsen, Ninna Aggerholm-Pedersen, Johnny Keller, Akmal Safwat, Steen Baerentzen, Alma Pedersen
Department of Experimental Clinical Oncology, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Oncology, Aarhus University Hospital; Department of Pathology, Aarhus University Hospital; Department of Clinical Epidemiology, Aarhus University Hospital
Background: To assess the excess mortality caused by
soft tissue sarcoma (STS), sarcoma-specific
estimates are often reported; however,
these rely on precise and correct data on
the cause of death, which can be difficult to
acquire. Another, more precise, method is to
assess the relative mortality, i.e., mortality in
sarcoma patients compared to the general
population.
Purpose / Aim of Study: The aims of this study were to assess the
relative mortality in STS patients, and to
compare this with the sarcoma-specific
mortality.
Materials and Methods: We included 1246 patients treated for STS at
the Aarhus Sarcoma Centre between 1979
and 2008, and 6230 individually age- and
sex-matched individuals from the general
population. The relative mortality was
estimated as rates and rate ratios, using the
Cox proportional hazard model. The
sarcoma-specific mortality was compared to
the corresponding relative mortality.
Findings / Results: The overall 5- and 10-year relative mortality
was 32.8% and 36.0% Overall, STS patients
had a 4.4 times higher risk of dying within
the first five years after diagnosis and a 1.6
times higher risk between five and ten years
compared with the general comparison
cohort. Patients with low-grade STS did not
have increased mortality compared with the
general population. The relative mortality
was highest in younger patients and in
patients without comorbidity. The overall 5-
year sarcoma-specific mortality was
underestimated by 3.1 percentage points
compared to the relative mortality.
Conclusions: Patients with low-grade STS did not have
increased mortality compared with the
general population. A tendency towards
underestimating mortality due to STS was
seen when sarcoma-specific mortality using
death certificates was reported.
54. Prognostic preoperative parameters for survival in patients treated by joint replacement surgery for extremity bone metastases
Michala Skovlund Sørensen, Klaus Hindsø, Kristine Grubbe Gregersen, Michael Mørk Petersen
Ortopædkirurgisk klinik, Rigshospitalet
Background: Estimation of patient survival is important
when planning surgical treatment of
metastatic bone disease (MBD) of the
extremities. We have done a single
centre study evaluating prognostic
preoperative parameters for patient
survival after joint replacement (JR)
surgery in patients with MDB of the
appendicular bones.
Purpose / Aim of Study: To estimate prognostic preoperative
parameters for patient survival, in
patients receiving JR, due to MBD in the
appendicular skeleton.
Materials and Methods: We included 130 patients that received a
JR due to MBD during the period Jan '03
to Dec '08 at the Department of
Orthopaedic Surgery, Rigshospitalet,
Copenhagen. The cohort was followed
with regard for survival until death or
marts 29th '11.
The following data were registered: age,
gender, pathological fracture/impending
fracture, number of bony metastases,
visceral metastases, erythrocyte
sedimentation rate (SR), C reactive
protein (CRP), haemoglobin (HGB),
Karnofsky score, ASA score, and
primary type of cancer.
Statistics: Kaplan-Meier survival analysis
with logrank test and Cox proportional
hazard regression analysis.
Findings / Results: The calculated probability of survival after
surgery was 51% and 39% at 6 months
and 1 years of follow-up. The median
survival time was 7 (0.03–96) months.
Univariate analysis showed that all
preoperative parameters were statistical
significant predictors for survival except
gender and pathological
fracture/impending fracture.
Multivariate analysis showed that
visceral metastasis, Karnofsky score <
7, ASA group 3 or 4, HGB < 8 and
primary type of cancer remained
statistical significant predictors of
survival.
Conclusions: We have been able to identify
preoperative parameters that correlate to
patient survival in patients operated on,
with a JR, because of MDB in the
appendicular skeleton.
55. YKL-40 protein expression in osteosarcoma tumor tissue
Andrea Thorn, Lise Hanne Christiansen, Søren Daugaard, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark
Background: YKL-40 is a glycoprotein that has showed
increased expression in several other types
of cells such as cancer cells, macrophages
and leukocytes, embryonic cells, fetal cells,
and cartilage cells. Previous studies have
shown that elevated serum concentrations
of YKL-40 in patients with various types of
cancer constitute an independent prognostic
variable for both short recurrence-free
interval and short overall survival.
Purpose / Aim of Study: The aim of this study is to identify if ykl-40
can serve as a surrogate marker for
prediction of the outcomes in patients with
high-grade osteosarcoma.
Materials and Methods: All patients diagnosed with a high-malignant
osteosarcoma of the extremities, spine or
trunk wall at the Department of Pathology,
Rigshospitalet during the years 2000-2010
were identified (n=86). Of these 48 patients
(mean age 26 (6-88) years, F/M= 29/19)
met criteria for inclusion in the study based
on data availability and biopsy sample size.
The biopsies were analysed by
immunohistochemical analysis in order to
determent the degree of YKL-40 staining
intensity in tumour tissue
Findings / Results: All 48 biopsies were positive for YKL-40
staining with various staining intensities. If
the mean staining intensity of 24% was
used to divide the material, we found a
better survival in patients with high staining
intensity (p=0.05), and the 5 and 10 years
survival was 80% for patients with a staining
intensity over the mean intensity of 24%
(n=15), and 48% and 43% respectively, for
patients with an intensity below the mean
(n=33)
Conclusions: Data indicates that a higher YKL-40
expression is connected to a longer overall
survival.
56. Survival of osteosarcoma patients diagnosed in East Denmark and treated at Rigshospitalet from 2000-2010.
Andrea Thorn, Søren Daugaard, Michael Mørk Petersen
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Denmark; Department of Pathology, Rigshospitalet, University of Copenhagen, Denmark
Background: Osteosarcoma is the most common
histological type of bone sarcomas.
Purpose / Aim of Study: To examine the overall survival for all
osteosarcoma patients diagnosed in East
Denmark and treated at Rigshospitalet from
2000-2010.
Materials and Methods: All patients diagnosed with a high-malignant
osteosarcoma at the Department of
Pathology, Rigshospitalet during the years
2000-2010 were identified (n=86). Sixteen
patients were excluded because it was
consultation biopsies from other hospitals
and 9 patients were excluded because the
diagnosis was later changed
(chondrosarcoma/giant cell
sarcoma/osteoblastoma/myeloma/ desmoid
fibromatose = 3/1/1/1/1), or was from before
2000 (n=2). A total of 61 patients (mean age
31 (6-88) years, F/M=34/27) were then
analyzed for survival. Survival data were
obtained from the CPR register. Statistics:
Kaplan Meier survival analysis and log-rank
test.
Findings / Results: The probability of 5 and 10-year survival for
all patients (n=61) was 57% and 52% years
respectively. The probability of survival in
young individuals (age ≤20 years) was not
different from patients aged >20 years
(p=0.14) and no difference between sexes
(p= 0.19) was found.
In patients treated with preoperative
chemotherapy (n=46) the survival was
higher (p=0.002), if the degree of tumor cell
necrosis was ≥90%. Both the probability of
5 and 10 years survival in patients with
≥90% necrosis (n=20) was 90%, while in
patients with <90% necrosis (n=26) survival
was 46% and 41% respectively.
Conclusions: The overall survival for patients with high-
malignant osteosarcoma in East Denmark is
consistent with the international average
overall survival for this patient group.
57. Pre-treatment biomarkers as prognosticators for mortality in patients with localized soft tissue sarcoma
Katja Maretty-Nielsen, Ninna Aggerholm-Pedersen, Johnny Keller, Alma Pedersen, Steen Baerentzen, Akmal Safwat
Department of Experimental Clinical Oncology, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Clinical Epidemiology, Aarhus University Hospital; Department of Pathology, Aarhus University Hospital; Department of Oncology, Aarhus University Hospital
Background: The existing literature on biomarkers and
mortality in soft tissue sarcoma (STS) is
limited in both number and size, lacking the
data on important confounders.
Purpose / Aim of Study: The aim of this study was to determine the
prognostic value of pre-treatment biomarkers
for mortality in a large population-based
series of adult patients with localized STS.
Materials and Methods: Pre-treatment levels of albumin, C-reactive
protein (CRP), hemoglobin, neutrophil to
lymphocyte ratio (NLR), and sodium were
analysed in 614 consecutive STS patients
treated at the Aarhus Sarcoma Centre
between 1994 and 2008. The prognostic
value of biomarkers on sarcoma-specific
mortality was estimated as hazard ratios
(HR) using Cox proportional hazard models
adjusted for important confounders including
age and comorbidity.
Findings / Results: Hypoalbuminemia (HR 1.85 [95% CI 1.14-
2.99]), anemia (HR 1.66 [95% CI 1.07-
2.56]), and elevated NLR (HR 1.72 [95%
CI 1.10-2.70]) were independently
associated with a statistical significant
increased mortality, while there where a
clear tendency towards CRP (HR 1.46
[95% CI 0.98-2.19]) being associated as
well. Patients with abnormal values in all
important biomarkers had a significant
additional risk of dying, compared to
patients with only some abnormal values
(HR 3.91 [95% CI 1.68-910]). The median
survival was 95.8 months in patients
with normal values compared to 30.7 and
7.2 in patients with only some abnormal
values, and patients with abnormal
values in all important biomarkers,
respectively.
Conclusions: Hypoalbuminemia, anemia, and elevated NLR
were independent prognosticators for early
death in patients with localized STS. The
measurement of these can be used as an
additional diagnostic tool to identify high-risk
patients that could be candidates for
possible intensive therapy.
58. Markedly reduced mortality following a major non-traumatic lower limb amputation
Morten Tange Kristensen, Gitte Holm, Michael Krasheninnikoff, Peter Gebuhr
Physical Medicine and Rehabilitation Research - Copenhagen, Depertments of Physiotherapy and Orthopa, Hvidovre University Hospital; Department of Orthopaedic Surgery, Hvidovre University Hospital
Background: Historically high 30-days and 1-year
mortality rates of respectively 30% and
54% were reported in a Danish 2009
consecutive series of 93 patients with
a non-traumatic lower limb amputation.
Purpose / Aim of Study: To evaluate if allocation of staff
expertise and instituting an optimized
program could reduce the number of
these fatal events.
Materials and Methods: A consecutive series of 129
amputations (median age of 75 (IQR,
65-84) years, 53% below knee (BKA)
and 47% amputated at a higher level
or bilateral (AKA), admitted to an
orthopaedic ward. The program
instigated within a 2-year period
included standards for fluid and
transfusion, supplemental oxygen
when supine, pain management, early
mobilization and physiotherapy, weekly
multidisciplinary meetings, and
monthly audits of standards.
Findings / Results: Twenty (16%) and 48 (37%) patients
respectively, died within 30-days and
1-year. Cox regression demonstrated
that a patient from a nursing home
(n=26) and/or an ASA-rating of 4 (n =
12) respectively, was 3 and 5 times
more likely to die within 30 days,
compared to a patient with an rating of
2 (n = 41), when adjusted for age,
gender, cause of and amputation level.
Length of stay was reduced with a
mean of 6 days.
Conclusions: Allocating people with expertise and
instituting an optimized program seem
to reduce the short and long-term
mortality rates markedly in patients
with a major lower limb amputation.
59. Tumor characteristics, patient reported symptoms and suspected and final diagnosis for 64 sarcoma patients referred to a sarcoma center after surgery/biopsy in non-specialist institutions.
Heidi Buvarp Dyrop, Peter Vedsted, Katja Maretty-Nielsen, Bjarne Hauge Hansen, Peter Holmberg Jørgensen, Johnny Keller
Department of Experimental Clinical Oncology, Aarhus University Hospital; The Research Unit for General Practice, Aarhus University; Department of Orthopaedics, Sarcoma Centre of Aarhus University Hospital
Background: Some sarcomas are referred after surgery
on suspected benign tumors. This can affect
patient prognosis and cause large re-
excisions. Knowledge about diagnostic
pathways of these patients is uncertain and
must be reviewed.
Purpose / Aim of Study: To investigate patient and tumor
characteristics, patient reported symptoms,
suspected and final diagnosis, and explore
reasons for referral, in sarcoma patients
referred after surgery in non-specialist
institutions.
Materials and Methods: Retrospective review of medical files. From
a previous study on 258 sarcoma patients
referred over 4 years, we identified 64
(24.8%) referred with a confirmed
histological sarcoma. Medical files were
reviewed for patient reported symptoms,
suspected diagnosis and reasons for
referral. Patient and tumor characteristics
were previously collected.
Findings / Results: 27 (42.2 %) tumors were low grade, 37
(57.8 %) high grade. Lipoma and
fibroma/dermatofibroma were most
reported suspected diagnoses. 7
patients were suspected of other
malignancies due to location (breast,
testicles, kidney). For 23 (35.9%)
patients, initial presence of alarm
symptoms were described in the referral
text. 9 tumors were >5cm, 10 subfascial
and 9 were both. 32 (50%) had
superficial small tumors, of which 21
(65.6%) were suspected skin conditions.
8 (12.5%) of 64 patients stated that it
was a second removal of a tumor in the
same area. 3 patients reported changes
in a tumor that had been present for
years.
Conclusions: 1/4 of sarcoma patients had surgery on
suspected benign tumors. For 1/3, alarm
symptoms had been reported, the remaining
fell outside referral guidelines or alarm
symptoms were not discovered. Sarcoma
should be considered even in unusual or
superficial locations, also when the tumor is
<5 cm. Recurring benign tumors and
changes in dormant tumors should cause re-
evaluation of diagnosis.
60. Factors predicting the basic amputee mobility outcome in patients with a major non-traumatic lower limb amputation.
Morten Tange Kristensen, Anni Østergaard Nielsen, Ulla Madsen Topp, Peter Gebuhr
Physical Medicine and Rehabilitation Research – Copenhagen, Departments of Physiotherapy and Orthopa, Hvidovre University Hospital; Department og Physiotherapy, Hvidovre University Hospital; Department of Orthopaedic Surgery, Hvidovre University Hospital
Background: Prosthetic fitting is the long term goal
for most patients following a major
lower limb amputation. However, this is
not possible in every dysvascular
amputee and not the primary focus of
today’s acute in-patient rehabilitation
programmes. On the contrary,
independence in transfers and
wheelchair skills is considered
mandatory for all, but knowledge
regarding who achieve this, and
factors influencing are limited.
Purpose / Aim of Study: To examine factors predicting the
basic amputee mobility outcome in an
acute orthopaedic ward following a
dysvascular major lower limb
amputation.
Materials and Methods: Ninety-one out of 103 (12 died in-
hospital) consecutive patients (32
women and 59 men, 57 below knee
and 34 above knee or bilateral index
amputations) with a mean age of 71.6
(SD, 12) years, admitted from their
own home. The outcome variables
were independency in bed- and bed to
chair transfers, and indoor wheelchair
manoeuvring.
Findings / Results: Patients who achieved independency
(n=64) stayed in the ward a mean of
23.2 (9.3) days as compared to 30.2
(20.2) for those not (30%). Multiple
logistic regression revealed that a
patient with no preamputation walking
ability was 6 times more likely not to
achieve independency in basic
activities during admittance, while odds
increased with 8% per each additional
year a patient got older, when adjusted
for gender, ASA-score, diabetes
(n=39) and the final amputation level.
Correspondingly, odds was 4 times
(P=0.06) higher for patients who
experienced a major revision or
reamputation (n=19).
Conclusions: The preamputation function and age
were independent predictors of the in-
hospital amputee mobility outcome,
while having a reamputation also seem
to influence. Clinicians, have the
possibility to spot patients who may
benefit from more intensive training,
while number of reamputations should
be reduced.