Paper 029
IN-DEPTH ANALYSIS OF WOUND COMPLICATIONS
FOLLOWING PREOPERATIVE RADIOTHERAPY
FOR LOWER EXTREMITY SOFT TISSUE SARCOMA
PATIENTS
Colleen Dickie, MSc1; Anthony M. Griffin3;
Joanne Moseley2; David Biau4; Amy Parent1;
Michael Sharpe1; Peter Chung1; Charles Catton1;
Peter C. Ferguson3; Jay S. Wunder3; Brian O'Sullivan1
1Department of Radiation Oncology, The Princess
Margaret Hospital Cancer Center, Toronto, ON, Canada;
2Radiation Medicine Department, The University of
Toronto, Toronto, ON, Canada; 3Division of Orthopaedic
Surgery, University Musculoskeletal Oncology Unit,
Mount Sinai Hospital, Toronto, ON, Canada; 4Service de
Chirurgie Orthopedique, Hopital Cochin, Paris, France
Objective: Wound complication (WC) rates were reduced
from 43% (phase 3 NCIC SR2 trial) to 30.5% in a recent
phase 2 study of preoperative intensity modulated radiotherapy
for lower extremity soft tissue sarcoma (IMRT trial).
The purpose of this study was to retrospectively analyze
all the elements of the volume of skin and subcutaneous
tissues used to close the resection site (surgical flaps-SF)
for patients in the IMRT trial and determine which parameters
were associated with WC.
Methods: 18 of 59 patients developed WC in the IMRT
trial. 8 patients were re-planned due to tumor growth; 5
developed WC. Surgeons delineated the SF on the RT
planning system (Pinnacle v9.0) for dose avoidance. A
MATLAB script and Pinnacle were used to quantify characteristics
of the SF contours including: RT dose, length,
volume, variable thickness across length/width, inclusion of
fascia, proportion of SF and planning target volume overlap
(SF overlap), and PTV and gross tumour volumes (GTV).
Study variables from the RT re-plan for the 8 growers were
analyzed separately and compared to the population. Univariate
and multivariate logistic regression models were
used to identify an association between relevant variables
and outcome.
Results: Table 1. Mean volume and width of SF was
significantly greater in the WC group compared to the
non-WC group. There was a trend towards a higher mean
SF dose, % SF receiving >30Gy, mean thickness/length,
and a closer mean tumor to skin surface (2.5 mm) in the
WC group. A significantly higher proportion of the SF received
the prescribed dose (SF overlap) in the WC group
(19% vs 8% non-WC group) which remained significant
on multivariate analysis (p=0.003). The WC group had
significantly larger GTV and PTV volumes (p=0.004 and
0.0002 respectively). There was no difference between the
groups for the proportion of fascio-cutaneous SF versus
subcutaneous SF. The growing population had significantly
larger GTV/PTVs, SF overlap (42%, p=0.00001), mean SF
dose, %SF receiving >30Gy, and a shorter mean tumor to
skin distance (2.2 mm).
Characteristics of Local Recurrence
Patient Histology Site Dim Max
(cm) Grade Margin Sequencing
of IMRT
Vrecur
95% IDL
LR
Category
1 Liposarcoma Thigh 25 Low Close/Positive Post-op 100% Central
2 Myxofibrosarcoma Thigh 10.5 High Close/Positive Post-op 100% Central
3 Myxofibrosarcoma Hand 1.6 High Close/Positive Pre-op 100% Central
4 Liposarcoma Thigh 18 High Close/Positive Post-op 100% Central
5 MFH Thigh 12 High Close/Positive Post-op 94.4% Marginal
6 MFH Thigh 15 High Negative Post-op 93.6% Marginal
7 MFH Thigh 15.3 High Negative Post-op 92.3% Marginal
8 STS (NOS) Arm 6.5 Low Negative Post-op 90.5% Marginal
9 STS (NOS) Thigh 5.1 High Close/Positive Post-op 74.1% Marginal
10 Fibrosarcoma Triceps 8 High Close/Positive Pre-op 35.3% Marginal
11 Myxofibrosarcoma Thigh 21 High Close/Positive Pre-op 18.5% Marginal
12 Myxofibrosarcoma Thigh 17.9 High Negative Post-op 0.1% Marginal
13 MFH Knee 6.6 High Close/Positive Pre-op 0% Distant
11 6
SF: Surgical Flaps WC: Wound Complications
RT: Radiotherapy
PTV: Radiotherapy Planning Target Volume
GTV: Gross Tumour Volume
Paper 030
IMRT, DESIGNED WITH EVIDENCE-BASED BONE
AVOIDANCE OBJECTIVES, REDUCES THE RISK
OF BONE FRACTURE IN THE MANAGEMENT OF
EXTREMITY SOFT TISSUE SARCOMA
Colleen Dickie, MSc1; Michael Sharpe2; Peter Chung1;
Anthony M. Griffin3; Amy Parent1; Charles Catton2;
Peter C. Ferguson3; Jay S. Wunder3; Brian O'Sullivan1
1Radiation Oncology, Princess Margaret Cancer
Center, Toronto, ON, Canada; 2Radiation Medicine
Department, The University of Toronto, Toronto, ON,
Canada;3Division of Orthopaedic Surgery, University
Musculoskeletal Oncology Unit, Mount Sinai Hospital,
Toronto, ON, Canada
Objective: To evaluate the potential for IMRT, designed
with evidence-based bone avoidance objectives (BAO), to
reduce the risk of radiation induced fracture in the combined
modality local treatment of extremity soft tissue sarcoma
(E-STS).
Methods: Our database was searched to determine the
number of E-STS patients treated with IMRT and limb sparing
surgery from July 2005 to March 2011 , and for those
who developed a fracture. E-STS IMRT approved plans (n =
230, 176 lower and 54 upper) were identified that employed
BAO established from a previous study (1). The IMRT
planning goal was to reduce the mean bone dose <37 Gy
and the maximum bone dose <59 Gy with target coverage
prioritized. Preoperative (pre-op) IMRT was used in 199
patients, and 27 were treated postoperatively (post-op), using
2 Gy per fraction over 5-6.5 weeks. Four patients were
re-irradiated for recurrent disease using a hyperfractionated
regime of 44 Gy delivered twice daily over 4 weeks. Mean
and max bone dose as well as mean CTV dose were evaluated
to ensure compliance with BAO and target coverage.
Conclusion: The observation that WCs are reduced when
at least 92% of the SF is proportionally excluded from the
PTV provides a volume estimate for IMRT optimization
which can minimize WC. Larger GTV/PTV volumes were
associated with a higher risk of WC, as was increasing
tumour volumes during RT.
Comparison of surgical flap (SF) characteristics
SF PARAMETER WC
GROUP
NON-WC
GROUP P-VALUE TUMOUR
GROWERS P-VALUE
Mean SF RT dose 33.1 Gy 31.7 Gy 0.43 39.1 Gy 0.003
Mean SF Volume 392.2 cc 237.7 cc 0.001 318.3 cc 0.59
Mean SF Width (right-left) 2.01 cm 1.70 cm 0.05 1.79 cm 0.99
Mean SF Length
(superior to inferior) 27.5 cm 25.0 cm 0.07 28.3 cm 0.35
Mean SF thickness
(Anterior-posterior) 2.02 cm 1.76 cm 0.24 1.56 cm 0.50
Tumour to Skin Proximity 2.5 mm 2.8 mm 0.38 2.2 mm 0.36
% PTV and SF overlap 19 % 8 % 0.0002 42 % 0.00001
GTV 886.7 cc 491.4 cc 0.004 11 93.7 cc 0.006
PTV 2430.3 cc 1451.5 cc 0.0002 2744.2 cc 0.009
% SF receiving > 30 Gy 65 % 61 % 0.41 85 % 0.002
Mean follow up was 41.2
months from the time of
surgery.
Results: For pre-op
IMRT: the mean dose
to bone, max bone dose
and CTV mean dose
were 26.9 ± 9 Gy, 50.7
± 4 Gy and 51.1 ± 1 Gy
respectively (with SD).
For post-op IMRT, these
measures were 31.7 ±
18 Gy, 55.4 ± 13 Gy and
64.5 ± 2 Gy respectively.
Target coverage criteria
were satisfied in all
cases. BAOs were achieved in 99% of pre-op and 75% of
post-op plans. Four patients experienced a bone fracture.
One patient had a local recurrence within the previous RT
volume and received further RT using the hyperfractionated
regime. One case failed the BAOs with a mean bone dose
of 40.1 Gy and the fracture site coinciding with the region of
max dose. The final two patients received pre-op RT with
the CTV > 90% circumferential around bone.
Conclusion: The overall risk of fracture (1.7%) appears
lower than our previously reported incidence of 6.3%.
The preferential use of pre-op IMRT underpins attention
to reduction in adverse RT morbidities associated
with larger treatment volumes and higher doses typically
used in the postoperative setting. The IMRT BAOs are
both practical and beneficial. Bone sparing IMRT should
be especially considered for circumferential disease
around bone and in re-irradiation settings.
1. Dickie CI et al. Bone fractures following external beam
radiotherapy...IJROBP. 2009;75(4):111 9-24.
11 7
Figure 1. Receiver operating characteristic (ROC) curve for
femur fracture in patients treated with adjuvant IMRT using
the PMH nomogram (blue line); reference line (green).
Paper 031
EVALUATION OF FEMUR FRACTURE RISK IN SOFT
TISSUE SARCOMA OF THE THIGH TREATED WITH
INTENSITY MODULATED RADIATION THERAPY
Michael R. Folkert, MD PhD1; Samuel Singer2;
Murray F. Brennan2; Patrick J. Boland3; Kaled M. Alektar1
1Radiation Oncology, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA; 2Surgery, Memorial
Sloan-Kettering Cancer Center, New York, NY, USA;
3Orthopedic Surgery, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA
Objective: To compare the observed risk of femoral
fracture in primary soft-tissue sarcoma (STS) of the thigh
treated with adjuvant IMRT to expected risk using the
Princess Margaret Hospital (PMH) nomogram.
Methods: Patients treated with adjuvant IMRT before 2009
for STS of the thigh were included (84); those receiving
prophylactic internal fixation were excluded (2). Expected
femoral fracture risk was calculated using the PMH nomogram,
which was based on a cohort of patients treated
principally with conventional radiation therapy. Cumulative
risk of fracture was estimated using Kaplan-Meier statistics.
Independent prognostic factors on multivariate (MVA)
analysis were identified using Cox's stepwise regression.
Results: Between 2/2002 and 11 /2009, 82 consecutive
eligible patients were included. Median followup was 44
months (range 6-129). Of the patients treated, 35 (43%)
were female. The average age was 57 years (range
19-88). Thigh compartment was anterior in 38 (46%)
Figure 2. Cumulative risk of fracture in patients with extremity
STS treated with IMRT.
patients, posterior in 26 (32%), and medial/adductor in
18 (22%) . The median tumor maximum dimension was
11 .3 cm (range 2.5-31 cm). Periosteal stripping was
performed in 19 (23%) patients. Preoperative IMRT to
50 Gy was delivered in 13 (16%) patients, and postoperative
IMRT was delivered in 69 (84%) patients to
a median dose of 63 Gy (range 59.4-66.6). Adjuvant
chemotherapy was administered in 31 (38%) patients.
There were 5 (6.1%) fractures. The median time to fracture
was 12.2 months (range 6.9-54.9). The PMH femur fracture
nomogram was predictive in the IMRT cohort (Fig 1). The
observed crude risk of fractures was 6.1% compared to
26.4% expected risk from the nomogram. The followup
duration in the current study (mean: 4.3 years) was shorter
than the PMH nomogram cohort (mean: 8.6 years), yet the
cumulative risk of fracture using IMRT at 5-years was still
8.6% (95% CI 0.6-16.6%) (Fig 2). Predictors of fracture on
univariate analysis were tumor size (P=.012) and extent of
periosteal stripping (P=.049). On MVA, these factors did
not retain significance.
Conclusion: In this study, the observed risk of femoral
fracture in patients treated with IMRT (6.1%) is less than
the expected risk using the PMH nomogram (26.4%). Longer
followup duration in the PMH cohort may contribute to
this difference, but even reporting cumulative 5-year risk
in the IMRT cohort, the rate was only 8.6%. Established
predictors of femoral fracture such as gender, age, tumor
size, and periosteal stripping seem to exert less influence
when using IMRT.