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Indian Journal of
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Volume 8 Number 2
July - December 2020
Original Articles
Case Reports
Contents
Dosimetric Analysis of Three Dimensional Conformal Radiation therapy and
Intensity Modulated Radiation therapy coplanar Plans for Patients with
Glioblastoma Multiforme ( GBM) 73
Sajad A. Rather, Ajaz A. Khan, Nayak B. Gull, M.Mohibul Haq, Mudasir A. Shah,
Misba H Baba, Mohsin R Khan, Nazir A. Dar
Aggressive Sebacous Carcinoma of Extremity : A Rare Case Report 85
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Subject Index 103
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Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
72
Indian Journal of Cancer Education and Research
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Indian Journal of Cancer Education and Research
Volume 8 Number 2, July - December 2020
DOI: http://dx.doi.org/10.21088/ijcer.2321.9815.8220.11
Original Article
Dosimetric Outcomes of Three Dimensional Conformal Radiation
therapy and Intensity Modulated Radiation therapy coplanar Plans for
Patients with Glioblastoma Multiforme ( GBM)
Sajad A. Rather1, Ajaz A. Khan2, Nayak B. Gull3, M.Mohibul Haq4, Mudasir A. Shah5,
Misba H Baba6, Mohsin R Khan7, Nazir A. Dar8
Author’s Affiliation: 1,Assistant Professor, 2Medical
Physicist,3Senior Resident,4Professor,5-7Research officer's,
8Statistician, 1,2,4,5,6,7Department of Radiological Physics and
Bio-Engineering, 3,8Department of Radiation Oncology, Sher-
i-Kashmir Institute of Medical Sciences, Srinagar 190011,
India
Corresponding Author: Sajad Ahmad Rather, Assistant
Professor, Department of Radiological Physics and Bio-
Engineering, Sher-i-Kashmir Institute of Medical Sciences,
Srinagar, India.
E -mail: sajadahmadrather56@gmail.com
Abstract
The aim of the present study is to evaluate the dosimetric analysis of doses received by planning target volume
and organs at risks by using intensity-modulated radiation therapy (IMRT) and three-dimensional conformal
radiation therapy (3D-CRT) techniques in patients treated for glioblastoma multiforme. A total of ten patients
underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion.
Prescription dose and normal-tissue constraints were identical for the 3DCRT and IMRT plans. All the Patients
were treated on Clinac DHX Linear Accelerator. The prescribed dose was 60 Gy delivered at 2.0 Gy per fraction
using 6 MV photons. The tolerance level for maximum dose was 7.0 Gy for lenses and 54.0 Gy for brain stem, optical
chiasm and optical nerves as per RTOG criteria. The Target volumes, organ at risk (OAR), dose volume constrains
were used for planning. Cumulative dose volume histogram of target volumes and organ at risk (OAR), normal
brain tissue integral dose, target coverage, target homogeneity, target conformity, and normal tissue sparing with
3DCRT and IMRT planning were compared. Statistical analysis was performed to determine the differences. A
statistically significant difference between 3DCRT and IMRT and in the mean dose to the PTV (p < 0.519) has been
observed. The mean value of the PTV was 61.04 ± 1.152 in 3DCRT and 60.72 ± 1.005 in IMRT. The maximum dose
to the PTV in 3DCRT (64.26 ± 2.36) and in IMRT (62.95 ± 2.33) had a lower maximum dose to the PTV (p = 0.228).
This result indicates that IMRT was better than 3DCRT. The average minimum dose in IMRT was (46.80 ± 3.89)
compared to (49.06 ± 4.98) in 3DCRT, (p = 0.285). The dose to 95% of the PTV was (57.73 ± 1.55) in IMRT to (58.20
± 0.97) in 3DCRT, (p = 0.423). Conformity index (CI) was approximately equal in both modalities with an average
value of 0.962 ± 0.041 in IMRT compared to (0.969 ± 0.039) in 3DCRT, (p = 0.481). The average homogeneity index
(HI) in IMRT was 0.187±0.176 and 0.099 ± 0.050 in 3DCRT, (p = 0.165). Therefore, IMRT achieved an improvement
in HI. Target coverage index (TCI) in IMRT was 0.7213 ± 0.2050 and 0.5970± 0.194 in 3DCRT. The IMRT plan yielded
superior target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability
of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while
minimizing toxicity, therefore potentially improving outcomes in patients with high-grade glioma.
Keywords: Glioblastoma multiforme (GBM), Intensity modulated radiation therapy (IMRT), Three dimentional
conformal radiation therapy (3DCRT).
How to cite this article:
Sajad A. Rather, Ajaz A. Khan, Nayak B. Gull et. al. Dosimetric Outcomes of Three Dimensional Conformal Radiation therapy
and Intensity Modulated Radiation therapy coplanar Plans for Patients with Glioblastoma Multiforme ( GBM). Indian J Canc Educ
Res 2020;8(2):9-14.
Introduction
Treatment for malignant gliomas typically requires
a combined approach that includes surgery,
radiotherapy and chemotherapy. Radiotherapy
is an important adjuvant treatment for malignant
gliomas. Intensity-modulated radiotherapy (IMRT)
has been demonstrated to be superior to three-
dimensional conformal radiotherapy (3D-CRT) in
patients with malignant gliomas.1-3 The treatment
of malignant gliomas after surgery has been
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
74
reportedtosignicantlyprolongpatientsurvival.4-6
With the introduction of modern techniques like
Three Dimensional Conformal Radiation therapy
(3D CRT) and Intensity-Modulated, the use of
Radiation therapy (IMRT) is increasing in clinical
practice.7-9 Modern radiotherapy techniques such
as3DCRTandIMRTsignicantlyincreasethedose
to the tumor and reduce the dose to the normal
tissue.10-12
Intensity modulated radiation therapy (IMRT)
uses computed tomography based planning and
delivery of radiation, and with the help of TPS
improves the dose to target , while minimizing doses
toorgansatrisk(OAR),itcanprovidesignicantly
better tumor target coverage and sparing of
sensitive normal tissue compared with 3D CRT.13-
14 Such modern techniques use modern medical
imaging techniques, efcient dosimetric software,
accurate patient positioning methods, stringent
verication and quality control of procedures,
which increases tumor control by boosting tumor
dose, reducing morbidity and sparing healthy
tissues.15 Three dimensional conformal radiation
therapy uses computed tomography planning to
generate 3D volumes of a patients’ anatomy. In 3D
CRT, multiple beams at various angles are projected
towards target in such a way that the intended
dose will be delivered to the target while relatively
sparing critical structures. 3D CRT often produces
unacceptable plans for concave or irregular targets
that are close to critical structures.16 In Intensity
modulated radiation therapy (IMRT) dynamic
or static multileaf collimators are used for dose
optimization and thus delivers highly conformal
dose to target while sparing the surrounding
normal structures. The multileaf collimator can be
in a “dynamic” or “static” form. In the dynamic
form, the leaves at each gantry position are swept
across the target while the beam is on and their
speed determines the radiation uency. In static
or segmental multileaf IMRT, each eld consists
of multiple segments with different intensities.
These forms of IMRT are currently offered by most
manufacturers of linear accelerators.17-19 Intensity
modulated radiation therapy (IMRT) requires
additional clinician input for delineating target
volumes and more robust physics actions has to
beperformed.Assessmentoftherisksandbenets
of IMRT is therefore important in determining its
clinical utility.17 The dose-volume-histogram (DVH)
is a common tool used in both IMRT and 3D CRT to
evaluate dose conformity and homogeneity to target
and at the same time this tool gives information
about the dose received by the critical structures.
DVHs do not provide spatial information such
as the location of the high- and low-dose regions
(“hot” and “cold” spots) inside the volume of
interest (VOI).18 Patient-specic quality assurance
(QA) is used to verify the dose mapping given by
the treatment planning system (TPS). Verication
procedures for 3D conformal radiation therapy
(3D CRT) and intensity-modulated radiotherapy
(IMRT) are commonly performed for an individual
patient.19
Materials and Methods
2.1. Planning Systems and Radiotherapy Machine
Clinac DHX was the linear accelerator used
for present study. It has 40 pairs of multi leaf
collimators, the width of each leaf when projected
at the isocenter is 10 mm. This linear accelerator
has two modes of treatment, photon mode and
electron mode. In this study only photon mode
with 6 MV energy is used. The treatment planning
system was the external beam planning system of
Eclipse (Varian Medical System) and the volume
calculation used was the Anisotropic Analytical
Algorithm (AAA).
2.2. Acquisition and Simulation
Planning CT scans were taken on Somatom
Sensation Siemens CT Simulator with patients
in supine position and immobilized with a three
clamp ort cast. Imaging acquisition protocol
required a slice thickness of 3 mm in a multislice
CT scanner, both immediately (within 15 s) and
delayed, in other words, 10 min after injection of
contrast. The images were then transferred to the
Eclipse™ treatment planning system (v. 13.2, Varian
Medical Systems, CA, USA). Planning CT images
were fused with postoperative magnetic resonance
(MR) images that were taken a few days before
starting the radiation. The target and other OAR’s
were contoured following RTOG protocol. The
gross tumor volume (GTV) included postoperative
cavity and gross residual tumor seen on the CT
images and fused MR images. The clinical target
volume (CTV) includes 2.0 cm isotropic margin all
around the GTV along with edema surrounding the
tumor following anatomical boundaries. PTV was
generated by giving a 0.5 cm symmetrical margin
around the CTV. OARs, including the optic chiasm,
right and left optic nerves, right and left temporal
lobes, brain stem, right and left eye, right and left
lens and right and left cochlea, were contoured.
Sajad A. Rather, Ajaz A. Khan, Nayak B. Gull et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
75
Plans were optimized to deliver prescribed dose
to more than 95% of PTV and maximum dose in
the target volume not to exceed 107% of prescribed
dose international commission on radiation units
and measurements (ICRU) : 50 and 62. Dose
volume histograms were generated for qualitative
and quantitative assessment of generated plans
and evaluated for all the OARs before delivering
treatment. Evaluation of dosimetric data was done,
in other words, doses received by target volumes
and OARs using Quantitative Analysis of Normal
Tissue Effects in Clinics (QUANTEC). If the dose
constraints of OARs were not met, depending on
the location and burden of the tumor, we prioritized
the OARs surrounding the tumor and plans were
optimized accordingly, for example, for tumors
close to or invading the left optic nerve, instead of
under dosage, we have preferred treating till 60 Gy
after prioritizing the right optic nerve to preserve
vision. All 3D-CRT plans were analyzed in terms of
PTV coverage, conformity index (CI), homogeneity
index (HI) and OAR dose volume parameters, as
per ICRU 83.
2.3. Conformal Planning
Treatment plans were created with 6 MV photons.
All elds were shaped at the beam’s eye view
to encompass the PTV shape using multileaf
collimator (MLC). The treatment target volume
included the PTV and an additional 0.7-cm margin
for beam penumbra in all directions. The treatment
eld’s isocenter was positioned in the center of
the PTV and the calculation point was taken at the
treatment eld’s isocenter. Physical wedges (PW)
and virtual wedges (VW) were used to modify the
dose in the treatment plan and to perform dose
homogeneity in PTV.
2.4. Inverse-Planned IMRT
Treatment plans were created for 6-MV photons
with the same TPs with objective functions based
on physical constraints. IMRT plans were generated
using commercial inverse planning software. The
beams are spread around the target with equispace
andtoavoidtheopposingeldsanoddnumbersof
thetreatmenteldswereused.
2.5. Treatment Planning Evaluation Tools
The TPS used for this study (Eclipse 13.2) have many
tools for qualitative and quantitative evaluation
of the treatment plans. The visual slice by slice
review of the treatment plans using isodose lines
distribution can be used as a qualitative evaluation
for the treatment plans. The qualitative evaluation
is important to know the location of the hot and
cold areas in the treatment plans. The quantitative
evaluation included the maximum, minimum, mean
doses and DVHs. Dose Volume Histogram (DVH)
was generated to evaluate the dose to the different
structures in different treatment plans. For PTV, the
parameters, D98%, D95% and D2% were used for
plan evaluation, where D98% and D2% values are
denedasthedosereceivedby98%and2%ofthe
PTV volume these two values are represented the
maximum and minimum doses in the PTV, D95%
is target volume covered by 95% of the prescribed
dose, for OARs, the mean and maximum dose for
brain stem, optic nerve and lenses were used for
treatment plan evaluation.
2.6. Comparative evaluation of treatment plans
In this study, dosimetric analysis of 3D CRT and
IMRT plans was performed for each of the 10
patients by both qualitative and quantitative
measures.Isodosedistributionwasrstcompared
visually on axial, sagittal and coronal slices for
degree of conformity of the prescribed dose to the
PTV and then for any inclusion of OAR within high
doseandlowdoselevels.Specically,weexamined
isodose lines from 5 Gy and up in our evaluation.
Direct comparison was also made of the cumulative
DVH curves for PTV, OAR, and non-target tissue.
Integral dose to non-target brain tissue (Brain-PTV)
was evaluated. Plan comparison was also made
quantitatively by comparing DVH parameters and
by computing and comparing relevant metrics
for target coverage, target conformity, dose
heterogeneity within the target, and critical normal
tissue sparing. Target coverage was assessed by
comparing the minimum and maximum doses to
PTV (Dmin and Dmax respectively).
The dosimetric evaluation metrics used to
compare the two plans, in terms of mean, maximum
and minimum doses to PTV, were dose to 95% of
PTV, Homogeneity Index (HI), Conformity Index
(CI), Target Coverage Index (TCI) and Mean and
maximum doses to critical organs and normal
tissue. The dose to 95% of the PTV (D95%) was used
to quantify PTV coverage. The homogeneity index
(HI) was used to evaluate uniformity (homogeneity)
of dose within the PTV and is calculated as
Dosimetric Outcomes of Three Dimensional Conformal Radiation therapy and Intensity Modulated Radiation
therapy coplanar Plans for Patients with Glioblastoma Multiforme ( GBM)
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
76
HI = D2% – D98%
D50%
(1)
Where D2% and D98% represent the doses to 2%
and 98% of the PTV, respectively. For example,
D98 indicates that at least 98% of the target volume
receives this dose, and hence D2% and D98% are
considered to be the maximum and minimum
doses, respectively.
The conformity index (CI) was also calculated
andcanbedenedasthedegreeofconformityof
the plans, which is a ratio of the PTV receiving 95%
of the prescribed dose divided by the volume of the
PTV. A CI value approaching 1 indicates a higher
degree of conformity.
CI = PTV95%PD
VPTV
(2)
The target coverage index (TCI) accounts for the
exact coverage of PTV in the treatment plan at the
prescribed dose as shown below:
TCI = PTVPD
PTV (3)
Where PTVPD is the PTV coverage at the
prescribed dose (PD) and PTV is the volume of
PTV. Target conformity index reports target dose
coverage as a value between 0 and 1. A value of
1 indicates an ideal plan with target coverage
by prescribed dose. However, a TCI value of 0
indicates the whole target volume is not covered by
the prescribed dose [20-21].
Statistical Analysis
Statistical analysis was done using a paired two-
tailed student‘t’ test. The test was applied to
calculate the difference between two means. A
valueof p≤0.05wasconsideredtobe statistically
signicant.
Results
Differences were recorded between those patients
who planned with 3D CRT and those who planned
with IMTR. Thus one patient was selected to
represent all other patients in this site for isodose
distribution comparison, dose volume histogram
(DVH) comparison, dosimetric results for the PTV
and dosimetric results for the critical organs. DVHs
gures include the PTV and critical organs for
each modality and show the percentage of the total
volume (y-axis) of each ROI receiving a specied
dose (x-axis) in units of Gy.
3.1. Glioblastoma (GBM) Cancer
Ten patients whose diagnosis with GBM received
60Gyper30fractionsgivenoncedailyvedaysper
week over a period of six weeks were included in
this study. CT Scans were performed for the whole
brain on a CT scanner with 0.3 cm slice thickness.
The patients were positioned supine, and straight
and level. A warm wet sheet of plastic mesh was
placedoverthefacetotaroundtheheadandwas
Sajad A. Rather, Ajaz A. Khan, Nayak B. Gull et. al.
Table 1.1: Evaluation metrics for PTV in terms of DMEAN , Dmax and Dmin covered 95% of the target
Patient Code Dmean(Gy) Dmax(Gy) Dmin(Gy) D95%(Gy)
3DCRT IMRT 3DCRT IMRT 3DCRT IMRT 3DCRT IMRT
01 60.00 61.21 64.88 62.36 52.58 53.70 58.10 57.60
02 61.15 60.50 67.18 67.00 54.46 51.70 59.10 57.00
03 60.00 59.75 68.28 64.53 47.52 39.70 56.21 58.29
04 62.00 60.00 64.00 63.80 41.50 44.19 57.40 54.23
05 59.72 60.68 62.53 61.3 56.72 50.09 58.23 59.57
06 60.02 59.32 65.43 64.47 41.87 48.00 59.30 58.00
07 61.00 62.08 63.50 62.50 46.11 46.60 58.11 59.70
08 61.00 59.88 64.63 64.00 49.45 43.60 59.50 58.50
09 63.00 62.00 61.50 60.00 50.60 45.50 58.20 57.50
10 62.53 61.90 60.75 59.45 49.86 44.95 57.80 56.92
Mean 61.04±1.15 60.72±1.00 64.26±2.36 62.95±2.33 49.06±4.98 46.80±4.16 58.20±0.97 57.73±1.55
P-value P<0.519 P<0.228 P<0.285 P<0.423
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
77
secured to the table to ensure that the patient is in
the correct position during each treatment session.
After the CT scan, the images were transferred to
the treatment planning system (TPS) to initiate the
planning. Table (1.1) shows the mean, max and
minimum dose that covered 95% of the target and
p-value of the target (PTV) for both modalities. The
prescribed dose was 60 Gy.
3.2. PTV
Astatisticallysignicantdifferencebetween3DCRT
and IMRT and in the mean dose to the PTV
(p < 0.519) has been observed. The mean value
of the PTV was 61.04 ± 1.152in 3DCRT and 60.72
± 1.005 in IMRT. The maximum dose to the PTV
in 3DCRT (64.26 ± 2.36) and in IMRT (62.95 ± 2.33)
had a lower maximum dose to the PTV (p = 0.228).
This result indicates that IMRT was better than
3DCRT. The average minimum dose in IMRT was
(46.80 ± 3.89) compared to (49.06 ± 4.98) in 3DCRT,
(p = 0.285). The dose to 95% of the PTV was (57.73
± 1.55) in IMRT to (58.20 ± 0.97) in 3DCRT, (p =
0.423). Conformity index (CI) was approximately
equal in both modalities with an average value of
0.962 ± 0.041 in IMRT compared to (0.969 ± 0.039) in
3DCRT, (p = 0.481). The average homogeneity index
(HI) in IMRT was 0.187±0.176 and 0.099 ± 0.050 in
3DCRT, (p = 0.165). Therefore, IMRT achieved an
improvement in HI. Target coverage index (TCI)
in IMRT was 0.7213 ± 0.2050 and 0.5970± 0.194 in
3DCRT (Table 1.2).
3.3. Isodose distribution and DVH analysis.
Isodose distributions for the IMRT and 3D-CRT
are displayed in gure 1 and 2. The 3DCRT plan
contained the PTV receiving greater than 108% of
the prescription dose, 65.3 Gy. This was not the case
in the IMRT plan, as the dose distribution within the
PTV was more homogeneous. There were hot spots
(doses greater than 63 Gy) in the lateral portion of
the PTV in the 3DCRT plan and in the upper portion
of the PTV in the IMRT plan. The distributions
showed comparable PTV dose coverage between
the two modalities. PTV conformity in the 3DCRT
plan appeared worse than in IMRT. The 30 Gy lines
extended farther to cover the brain in IMRT than in
the 3DCRT plan. However, a small region of PTV
in the 3DCRT plan was receiving 65 Gy or greater,
the PTV dose conformity was greater in the IMRT
DVH provides useful quantitative dose assessment
by direct visual inspection of the dose curve [18].
Figure 3 contains a DVH for the 3DCRT and IMRT
plans. The y-axes of a DVH, specically for the
PTV, represent the region where the curve bends
away from 100% and “falls off” with the curve
maintaining a constant slope. The IMRT plan
Table 1.2. Evaluation metrics for the PTV in terms of CI, HI and TCI
Patient
Code CI = PTV95%PD
VPTV
HI = D2% – D98%
D50%
TCI = PTVPD
PTV
3DCRT IMRT 3DCRT IMRT 3DCRT IMRT
01 1.00 0.94 0.06 0.16 0.82 0.68
02 0.99 0.98 0.10 0.14 0.85 0.81
03 0.90 0.99 0.17 0.66 0.46 0.37
04 1.00 0.90 0.06 0.21 0.37 0.73
05 1.00 0.99 0.08 0.05 0.57 0.91
06 0.99 1.00 0.08 0.02 0.46 0.46
07 0.98 0.88 0.21 0.13 0.68 0.53
08 0.99 0.99 0.06 0.15 0.43 0.95
09 0.95 0.97 0.07 0.20 0.45 0.09
10 0.99 0.98 0.09 0.15 0.88 0.87
Mean 0.97±0.039 0.96±0.041 0.98±0.050 0.18±0.176 0.59±0.194 0.72±0.0.20
P-value P<0.481 P<0.165 P<0.143
Dosimetric Outcomes of Three Dimensional Conformal Radiation therapy and Intensity Modulated Radiation
therapy coplanar Plans for Patients with Glioblastoma Multiforme ( GBM)
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
78
Figure 1: Isodose distribution of patient Rt. parieto-occipital glioma planned with (A) 3DCRT (B) IMRT.
Figure 2: Isodose distribution of patient Rt. parieto-occipital glioma planned with (A) 3DCRT (B) IMRT.
Figure 3: Cumulative dose volume histogram of patient with postoperative malignant glioma in the right
parietal lobe glioma. (A) 3DCRT (B) IMRT.
Sajad A. Rather, Ajaz A. Khan, Nayak B. Gull et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
79
contained a broader region in the PTV, which
indicates higher dose coverage compared with
3DCRT. The PTV had a sharper falloff in the
IMRT plan representing the superior PTV dose
homogeneity observed in the isodose distributions.
DVHs showed a low dose to optic chiasm, optic
nerve, left and right lens and left eye in the IMRT
plan comparable to that of 3DCRT, and also a low
dose to the brain stem, spinal cord, right eye and
right optic nerve in IMRT.
Discussion
Patientswithcerebralmalignantgliomasclassied
as grade III or IV according to the WHO grading
system which account for three-fourths of all
glioma cases, were included in this study. Surgery
is the rst choice of treatment, but because of
inltrative growth and no obvious boundaries
with the surrounding normal tissue in higher
grade malignant glio¬mas, coupled with the
peculiarity of the anatom¬ical location, complete
surgicalresectionisoftendifcultifnotimpossible.
Postoperative radiation therapy has been used
as conventional treatment for malignant gliomas
with the radiation dose generally being 60 Gy, at
1.8–2.0 Gy per fraction. There has been a dramatic
improvement in radiotherapy techniques over
the last two decades. Improvements in dose
distribution and local control have been observed
with 3DCRT as compared with conventional two
dimensional treatment planning. It has also been
showed that the morbidity of therapy decreased
with the use of 3DCRT compared with conventional
treatment planning. Furthermore, IMRT has shown
improvement in target dose conformity, as well
as reduction in the dose to the normal tissues
while achieving comparable target coverage
when compared with 3DCRT techniques in many
treatment sites including esophagus, prostate,
paranasal sinuses, nasopharynx and other head
and neck sites [1,4,8-11].
In case of treatment of malignant glioma with
standard therapy consisting of maximal safe
surgical resection followed by involved eld
radiation therapy and chemotherapy has shown
survival advantage in favourable prognostic
groups. Uncertainties in target volume denition
may not only result in marginal misses of tumor
but also in unnecessarily overdosing the normal
brain. The recent developments in CNS imaging
technology like CT and MRI fusion in radiotherapy
planning and functional imaging may further
increases the ability to more precisely dene the
target volume and target the areas at risk of failure.
If gliomas can accurately mapped, IMRT may
provide further advantage because of its ability
to target selected more resistance parts within
the tumor with higher radiation doses without
increasing the dose to normal tissue. As the number
of long term survivors increases, an increase will
almost certainly be seen in the number of patients
suffering from the late effect of radiation. Therefore
to ensure optimal coverage with minimal radiation
injury, investigating the integration of advanced,
highly conformal radiotherapy techniques for this
disease is important. This study was a comparative
dosimetric evaluation of IMRT and 3DCRT for
treatment of ten patients of malignant glioma, with
respect to target coverage, conformity of prescribed
dose volume, sparing of organ at risk and integral
dose to non-target normal brain tissue.
Comparison of IMRT and 3DCRT for the
malignant glioma of the brain are scarce in
literature [5,12]. Chan et. al. with a study, group of
5 patients demonstrated that, simultaneous boost
in IMRT delivered higher dose to the gross tumor
volume while respecting same critical normal tissue
constraint and also still maintaining the uninvolved
normal brain tissue at dose levels of the 3DCRT .
One more study by Narayana et. al. analyzed 20
patients, showed that regardless of tumor location
IMRT did not lead to signicant improvement in
target coverage (maximum dose, minimum dose
,or D95 coverage) when compared to 3DCRT . Our
dosimetric analysis conrmed that there was no
signicant difference in target coverage between
IMRT and 3DCRT plans with slight superiority in
3DCRT plan in the range of 95%-100% of prescribed
dose. Both techniques were shown good
target coverage in initial PTV and boost PTV. For
many gliomas target coverage and dose uniformity
are excellent with standard 3DCRT techniques
owing to the nearly spherical or cylindrical shape
of the lesion. Therefore it was not surprising that
signicantfurtherimprovementwasnotobserved
with IMRT. Target coverage and dose uniformity
improvement with IMRT have been primarily
reported in sights like Head and Neck or Prostate
[8, 9], where the target is concave, surrounding
normal tissues with dose limits much less than that
of the tumor. Gliomas can be highly irregular but
typically exhibit few concavities. When concavities
do exist such as when the tumors surrounds the
chiasm the required dose gradient between tumor
and normal tissues is often less than that observed
in other sites. As a result very good target coverage
is often achieved with 3D planning. However as we
Dosimetric Outcomes of Three Dimensional Conformal Radiation therapy and Intensity Modulated Radiation
therapy coplanar Plans for Patients with Glioblastoma Multiforme ( GBM)
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
80
escalate the prescription dose for this tumors even
if only to areas of suspected high tumor density,
thebenetofIMRTmightincreasebecausesteeper
dose gradients and more concave dose distributions
will be necessary. Our study showed almost similar
dose uniformity within the target volume both in
3DCRT and IMRT as indicated by high degree of
dose uniformity.
Our data are comparable to those reported
by Hermanto et. al. where IMRT did not further
improve target coverage or dose uniformity within
thetarget,butitdidresultsinstatisticallysignicant
superiority in target conformity (p<0.001), and also
signicant reduction in the mean and maximum
doses to the critical structures like brain stem ,
optic pathway (p<0.05). In IMRT if the normal
structures like eloquent cortex, brain stem and
optic pathway is located near the target, there is
actually a compromise to be done in normal tissue
sparing and target coverage in the range of 95%-
100% of prescribed dose, because if we optimize
stringent dose constraint for normal tissue located
nearby target it was trying to create cold spot
within the target. Dose received by the 50% of the
volume of critical normal tissue was improved in
IMRT plans compared to 3DCRT plan. The integral
dose was evaluated for Brain-PTV, the average
normal brain tissue integral dose was reduced in
IMRT compared with 3DCRT by approximately
8%. These nding are comparable with majority
of the published studies. A study by Hermanto et.
al. [25], demonstrated IMRT decreased the total
integral dose to the non-target brain tissue by 7%-
10%, Narayana et. al. [23], reported a 7% decrease
in mean dose to normal brain with IMRT compared
with 3DCRT. In our study, 90% of the patients had
absolute reduction of integral dose with IMRT and
only about 10% of patient showed high integral
dose. The reason for this could be in those cases
the tumor was located eccentrically in the occipital
lobe and this was adequately covered with two
elds with 3DCRT techniques, whereas for the
treatment of the same target with IMRT multiple
eldsat different angulationsneed to beselected.
The passage of beams through larger depth might
tend to increase the integral dose to non-target
brain. It together underscores the fact that with
careful IMRT planning integral dose to the normal
tissuescanbesignicantlydecreased.Withcareful
planning in regard to choice of beam angles, beam
weighting, and recognition of potential exposure
of normal tissues to exit dose, our study showed
that IMRT enabled improvement in target dose
conformity, critical tissue sparing, and reduction of
integral dose.
This superior dosimetric advantage of IMRT may
prove useful in reducing dose to the surrounding
critical structures when tumor is situated very close
to these structures, in minimizing the treatment
relatedmorbiditylikecognitiondecit,toimprove
quality of life and also may have an option to re-
irradiate for recurrence of tumor when indicated in
long time survivors.
Conclusions
In the present study, target dose coverage was
improved with IMRT planning as compared with
3D-CRT planning, and dose to normal structures
was concomitantly decreased. With careful planning
and judicious selection of beam parameters, IMRT
improved target conformity and sparing of critical
normal tissues, without increasing the integral dose
and low-dose volume in patients with high-grade
gliomas. New diagnostic and therapeutic tools
hold promise for improving outcomes in patients
with high-grade glioma. Combining modern
tumor imaging technology with IMRT will permit
moreaccuratetumordenitionandradiationdose
intensicationwithoutincreasinginjurytonormal
brain and adjacent critical structures. Moreover, in
the era of more effective systemic treatments and
an increased number of long-term survivors, the
use of IMRT may minimize toxicity and improve
quality of life.
Conict of interest: Nil
Source of Funding: Nil
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Volume 8 Number 2, July - December 2020
DOI: http://dx.doi.org/10.21088/ijcer.2321.9815.8120.11
Case Report
Aggressive Sebacous Carcinoma of Extremity :
A Rare Case Report
Amresh Kumar, Jayeeta Sen, Vividha Dubey, Saurabh Karnawat, Virendra
Author’s Affiliation: 1-3Registrar, 4Associat Professor,
5Professor, Department of Radiation Oncology, Sri Aurobindo
Medical College & PG Institute, Indore, India.
Corresponding Author: Virendra Bhandari, Professor,
Department of Radiation Oncology, Sri Aurobindo Medical
College & PG Institute, Indore, India.
E -mail: virencancer@yahoo.co.in
Abstract
Sebaceous carcinoma is an uncommon aggressive malignant tumour derived from the adnexal epithelium of
sebaceous gland either from ocular or extraocular sites.
Extraocular sebaceous carcinoma is a rare malignancy when compared to periocular variant. The aggressive
types of extraocular sebaceous neoplasm are reported with lymph node and visceral metastasis associated with
poor prognosis. Here we report a case of aggressive recurrent extraocular sebaceous cell carcinoma of palm (upper
extremity) with recurrence to post op site and ipsilateral axillary lymph node metastasis.1
Keywords: Sebaceous Carcinoma, Upper Extremity.
How to cite this article:
Amresh Kumar, Jayeeta Sen, Vividha Dubey et. al. Aggressive Sebacous Carcinoma of Extremity : A Rare Case Report. Indian J
Canc Educ Res 2020;8(1):15-22.
Introduction
Sebaceous carcinoma, rst described by Allaire
in 1891 accounts for less than 1% of all cutaneous
malignancies.2 Sebaceous carcinoma either be
ocular(75%) or extraocular3 types (25%)4 Extraocular
sebaceous carcinoma has been reported more
commonly on the head and neck region4&5 followed
by trunk, salivary glands, genitalia, breast, ear
canal and intra oral cavity. Extraocular sebaceous
carcinoma involving trunk or extremity is very
rare but aggressive malignant tumour arising from
sebaceous glands. It is more common in sixth decade
of life (mean-63years) with no sex predilection.6
Which is also evident with our patient reported at
the age of 65 years.
Case Report
A 62 year, old male, presented to us with a complaint
of swelling over left forearm which was gradually
progressive since 5-6 months. On examination
there was a single, non tender, well dened and
demarcated swelling over subcutaneous plane of
ulnar aspect of forearm with no discharge / bleed.
His past medical history was unremarkable and
there is no family history of similar lesion or any
malignancy. Biopsy revealed poorly differentiated
carcinoma. Patient then underwent resection
with negative surgical margins and histology was
inconclusive.
The patient presented after 2 months after resection
with complaint of appearance of a nodular swelling
5 x 3 cm, skin coloured, hard without any signs of
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
86
inammationover skinof leftaxillary regionand
ipsilateral axillary lymph node metastasis (g 1).
A subcutaneous soft tissue nodular lesion 3 x 2 cm
on lateral aspect of palmar region, left hand and
two other soft tissue lesion 1 x 1 cm at anterolateral
aspect of left 4th metacarpophalangeal joint.
Patient underwent amputation of left forearm
along with left axillary lymph node dissection
(g 2). The frozen section revealed skin adnexal
carcinoma with involvement of medical resection
margin shows tumour deposits. In frozen section,
tumour composed of round to polygonal cells with
high N:C ratio, hyperchromatic nuclei, scanty to
moderate cytoplasm; forming lobules, cords and
acini, inltrating subcutaneous tissue (g 3). The
postoperative course was uneventful. The analysis
of surgical specimen revealed sebaceous carcinoma
(Grade2)(g 4). Lefthand with metastasisto left
axillary lymph node with extra nodal extension (pT4
N1bMx).Tumour inltrating overlyingskin with
ulceration LVE +, PNI +, left axillary matted lymph
node level 1 and 2 show metastasis with extra nodal
extension. Left axillary level 2 lymph node (2/18)
showed tumour metastasis. Patient was planned
for 1 cycle neoadjuvant chemo with Paclitaxel and
Carboplatin followed by EBRT to axilla and then to
continue chemo with Paclitaxel and Carboplatin but
patient delayed the treatment and reported after 1
and 1/2 month of amputation, to us with multiple
tiny nodules over exor aspect of amputated (g
7) left forearm (cutaneous metastasis) then he was
planned for EBRT to axilla by photons and EBRT
to forearm by electron followed by chemotherapy.
Patient was taken to mould room for preparation
of mould (g 5) to ensure immobilization during
the course of treatment. After CT simulation with
proper immobilization technique, treatment plan
was generated with contoured target volumes
and organ at risk. (Fig 6) He was planned for a
prescription dose of 54 Gy/30# (@1.8 Gy/#) to left
axilla and 60 Gy/30# (@ 2 Gy/#) to arm using 6
MV photon on DMX Varian Linear accelerator. He
tolerated the treatment well. (g 8) And is now
being treated with chemotherapy with Paclitaxel
and carboplatin.
Amresh Kumar, Jayeeta Sen, Vividha Dubey et. al.
Fig 1 : Frozen Section Histopathology Image
Fig 2 : Post Op Histopathology Image
Fig 3 : Mould Preparation
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
87Aggressive Sebacous Carcinoma of Extremity : A Rare Case Report
Fig 7 : Nodular Swelling Lt hand Before Excision
Fig 8 : Nodular Excised Tumor
Discussion
Extra ocular sebaceous carcinoma involving the
extremity is very uncommon, aggressive malignant
tumor arising from sebaceous glands. Mean age
of occurrence is 63 years involving both sexes in
equal proportion. The disease exhibits a variety
of histologic growth patterns and diverse clinical
presentation that diagnosis is often delayed for
months to years.7 The most frequent clinical
presentation is a painless subcutaneous rm
nodules (79%) located in dermis or hypodermics
of variable size (0.5to 5cm). Our patient reported to
us with a similar presentation of painless swelling.
Sebaceous carcinoma of extremity can also present
as pedunculated lesions, irregular mass or diffuse
thickening of skin. This protean appearance
frequently masquerades as other benign tumours or
inammatoryconditions, thereby leading to delay
Fig 4 : CT Simulation
Fig 5 : Image of Amputated arm During Course of Radiotherapy
Fig 6 : Image of Amputated arm After Completion of Radiotherapy
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
88
in diagnosis, inappropriate treatment, increased
morbidity and mortality. The lesions usually
present as pink to red yellow nodular growth in skin
and may clinically resemble pyogenic granuloma,
haemangioma or squamous cell carcinoma. The
draining lymph nodes may be involved in few
cases only like in our case.
Regardless of the location, this malignancy is
highly aggressive with a potential for regional
and distant metastasis. Our patient also presented
with recurrence of multiple cutaneous nodules at
post op site along with ipsilateral axillary lymph
node metastasis although there was neither
distant metastasis nor any sign of internal visceral
malignancy.
Sebaceouscarcinomahistologicallymaybeclassied
as well, moderately or poorly differentiated.
The morphological hallmark of sebaceous
differentiation is the detection of sebaceous cells
and demonstration of fat in vacuolated tumour
cells. Other differential diagnosis includes basal
cell carcinoma with sebaceous differentiation for
poorly differentiated sebaceous cell carcinoma.
Basal cell carcinoma exhibit peripheral palisading
and clefting from the adjacent stroma.
Sebaceous carcinoma express immunohistochemical
markers such as cytokeratin, epithelial membrane
antigen(EMA), Cam 5.2 and anti breast carcinoma
associated antigen-225 antibody.
The common associations of sebaceous carcinoma
are Muir-Torre syndrome; an autosomal dominant
condition comprising of sebaceous neoplasm with
one or more low grade visceral malignancies and
Nevus sebaceous of Jadassohn8 in the absence of
other participating factors such as radiotherapy
and AIDS.9
Distant metastasis and recurrence rates are more
common in the ocular type of sebaceous carcinoma
[3,10] when compared to extraocular sebaceous
carcinoma.
Treatment of sebaceous carcinoma requires wide
local excision with removal of involved regional
lymph nodes. But Nelson showed that the chances
of local recurrence are very high as seen in our
patient also.11 Bailet reported a review of 92 patients
with extraocular sebaceous carcinoma and found a
recurrence rate of 28% and metastasis in 21% of cases
after local excision.12 Bhandari V13 also reported a
case report of sebaceous carcinoma focussing on
its aggressive nature where limited response was
seen after chemotherapy. Radiotherapy has been
considered as an adjunctive or palliative treatment
but is generally not recommended as a primary
treatment. The role of chemotherapy has not been
denedduetoscarcityoftheselesion
Conclusion
Extraocular sebaceous carcinoma is a rare
malignancy; the arm localisation is even rarer. This
is an uncommon but aggressive malignant tumour
with higher incidence of recurrence and distant
metastasis. The diagnosis is essentially histological;
the treatment of choice is radical surgery. More
diagnosed is early and more the surgery is extensive
more the prognosis is better. Regular follow up is
necessary to detect local recurrence, locoregional or
metastatic spread.
Reference
1. https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3481818/
2. Ghosh SK, Bandyopadhyay D, Gupta S, Chatterjee
G, Ghosh A. Rapidly Growing Extraocular
Sebaceous Carcinoma Occurring During
Pregnancy: A Case Report. Dermatol Online J.
2008;14:8.
3. Nelson BR, Hamlet KR, Gillard M, Railan D,
Johnson TM. Sebaceous carcinoma. J Am Acad
Dermatol. 1995;33:1–15.
4. Wick MR, Goellner JR, Wolfe JT, 3rd, Su WP.
Adnexal carcinomas of the skin. II. Extraocular
sebaceous carcinomas. Cancer. 1985;56:1163–72.
5. Lazar AJ, Lyle S, Calonje E. Sebaceous neoplasia
and Torre-Muir syndrome. Curr Diagn Pathol.
2007;13:301–19.
6. Graham RM,Mckee PH, Megibbon D. Sebaceous
carcinoma. Clinical Exp Dermatol.1984;9:466-471
7. Sudip Ghosh, Debabrata Bandyopadhyay,
Sandip Gupta, Rapidly growing extra sebaceous
carcinoma occurring during pregnancy: A case
report. Dermatology online journal. 14(8): 8
8. Schwartz RA, Torre DP. The Muir-Torre
syndrome: A 25-year retrospect. J Am Acad
Dermatol. 1995;33:90–104.
9. Pettey A, Walsh J. Muir – Torre Syndrome : a case
report and review of the literature. Cutis. 2005; 75
: 149-155
10. Muqit MM, Roberts F, Lee WR, Kemp E. Improved
survival rates in Sebaceous Carcinoma of the
eyelid. Eye. 2004;18:49–53.
11. Nelson BR, Hamlet KR, Gillard M, Johnson TM.
Sabeceous carcinoma. Jam Acad Dermatol. 1995;
33(1): 1-15
12. Bailet JW, Zimmerman MC, Arnstein DP,
Wollman JS, Mickel RA. Sebaceous carcinoma
of the head and neck. Case report and literature
Amresh Kumar, Jayeeta Sen, Vividha Dubey et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
89
review. Arch Otolaryngeal Head Neck Surg. 1992;
118(11) : 1254 – 1249
13. 1.Bhandari V. Sebaceous carcinoma of the
extremity : a rare case report. Ijcer. 2013;Vol1(1095):
25-27.
Aggressive Sebacous Carcinoma of Extremity : A Rare Case Report
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
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Indian Journal of Cancer Education and Research
Volume 8 Number 2, July - December 2020
DOI: http://dx.doi.org/10.21088/ijcer.2321.9815.8120.3
Case Report
Extra Corporeal Irradiation to Treat Osteosarcoma at a Tertiary care
Institute in Central India: A Case Report
Jayeeta Sen, Amresh Kumar, Vividha Dubey, Saurabh Karnawat, Virendra Bhandari
Author’s Affiliation: 1-3Registrar, 4Associate Professor,
5Professor, Department of Radiation Oncology, Sri Aurobindo
Medical College & PG Institute, Indore, India. 453555
Corresponding Author: Virendra Bhandari, Professor,
Department of Radiation Oncology, Sri Aurobindo
Medical College & PG Institute, Indore, India. 453555
E -mail: virencancer@yahoo.co.in
Abstract
Extra corporeal irradiation (ECI) is a rarely employed technique of irradiation in malignant bone tumour. In
this procedure post en-bloc resection of bone it is irradiated with a dose of 50Gy in a single fraction and then it is
reimplanted. This procedure ensures high rate of local control, better anatomical fit and functional outcome. In this
case report we present the first case of extracorporeal irradiation in central India.
Keywords: Extra corporeal irradiation, malignant bone tumour, osteosarcoma.
How to cite this article:
Jayeeta Sen, Amresh Kumar, Vividha Dubey et. al. Extra Corporeal Irradiation to Treat Osteosarcoma at a Tertiary care Institute
in Central India: A Case Report. Indian J Canc Educ Res 2020;8(1):23-27.
Introduction
Malignant primary bone tumours are relatively
a rareentity. These are most commonly seen
in children and adolescent.1 The incidence of
osteosarcoma cases are 4-5 per 1000000.2-5
The treatment of osteosarcoma requires
multimodality approach for optimal management,
requiring expertise of surgical oncologist, radiation
oncologist, medical oncologist. The management of
malignant bone tumours (MBT) have undergone
immense advancement in last two decades. During
the initial days of oncology, the preferred treatment
of MBT was surgical resection (amputation). A
shift in treatment strategy was developed with the
aim of limb salvage. This treatment modality for
limb preservation aims at better local control of
the tumour and reconstruction of the limb which
wouldresult in restoration of organ function leading
to better quality of life and an improved survival.
Theprinciplewefollowhere,rstlywedoen-bloc
resection of the involved segment of the bone. After
which removal of all the grossly and macroscopically
present tumour over the bone segmentfollowed by
extracorporeal irradiation (ECI) of the bone segment
to achieve maximumtumoricidal effectalong
with sterilization and then re-implantation of
the bone into the body. ECI achieves maximum
tumour kill and also sterilizes the bone. Some of
the techniques employed for sterilisation of bone
before re-implanting it areautoclaving, microwave,
pasteurizing, liquid nitrogen, and radiotherapy
(extracorporeal radiotherapy).6-10 With ECI we
deliver a very high dose of radiation (50-300 Gy)
in single fraction which results in maximum
tumoricidal effect. With this case report we tried to
analysethepotentialbenetsandlimitationsfaced
during implementation of ECI at our institute.
Case Report
A 38-year-old, female, presented to us with initial
complaint of swelling over lower end right thigh
since 3 years. It was gradually progressive in
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
94
nature with no complaint of pain over the swelling
initially.Shehadnodifcultyinlimbmovementin
the beginning. Eventually she started to experience
pain while sitting in cross legged position since 2
years. On local examination there was a swelling
over the lower third of right thigh involving the
anterio-lateral region of the thigh. Swelling was
around 12 × 15 cms, well-dened margins, hard,
xed, non-tender. No popliteal lymph nodes or
inguinal lymph nodes were found on palpation.
Initial x-ray showed a large mass over her right
distal end of femur. (gure 1). MRI distal knee
joint suggestive of large mass lesion with soft
tissue and calcic component seen in distal thigh
arising from cortex of metaphyseal region of distal
femur posteriorly and posterior-laterally. No
surrounding marrow oedema or extension of lesion
intomedullarycavity.Nosignicantinltrationof
lesion into adjacent muscles which are displaced
peripherally by lesion. Increased uid seen in
suprapatellar bursa. Findings suggestive of
malignancy? Paraosteal osteosarcoma. Biopsy from
the right thigh swelling suggestive of conventional
osteosarcoma. Her CT scan chest was suggestive of
few sub centimetric nodules in bilateral lung bases.
The patient also underwent whole body scintigraphy
scan which was suggestive of increased uptake of
distal end of right femur. And no other evidence of
distal skeletal metastasis. Her biopsy block review
reportedparostealosteosarcoma(gure2).
The patient did not seek any medical care and
reportedvemonthslatertous.Afterafullroutine
and metastatic work up which revealed no evidence
for lung metastasis or distant metastasis? She was
started with neoadjuvant chemotherapy plan
according to OGS-12 protocol. Received four cycles
ofneoadjuvantchemotherapy,rsttwocycleswith
cisplatin and doxorubicin for three days and then
she was switched to ifosfamide and doxorubicin
for three days for next two cycles.Post completion
of her neoadjuvant chemotherapy her CT scan
Rightlowerlimb(gure3)wassuggestiveofspace
occupying lesion of size 10.4 × 8 × 12 cms in the
distal portion of right thigh arising from the right
posterolateral parosteal aspect of femur showing
areas of dense bony calcication mingled with
soft tissue component.No obvious intramedullary
component. The lesion is 1.5 cms proximal from
the knee joint. The goal behind multi-disciplinary
treatment approach at our institute is the best
treatment for the patient utilising all the speciality.
The patient post chemo was referred foronco-
surgery and radiation oncology opinion where she
was planned for wide local excision along with
extra corporeal irradiation.
For extra corporeal irradiation the involved segment
of bone was excised, all the grossly involved tumour
over the bone was removed (gure 4), in order
prevent contamination it was then transferred to a
different sterile tray over a different trolley where
atrst itcleaned withnormal saline,all the bone
marrow present in the excised section was removed
using suction and thenwrapped with a layer sterile
wetdrapesoakedwith2gmofvancomycin(gure
5) and then another two-layer surgical plastic
packing. The thickness of wrapping around the
bonesegment was of 3cm. The wrapping ensured
no air gaps were left and would help in achieving
homogenous dose distribution. The 3 cm of
layeredwrappinghelped us achieve the ‘build-up’
effect to the bone. The sealed segment of bonewas
transferred to Computed tomography (CT) console
for imaging and then the images were transferred
to treatment planning system (TPS). Eclipse version
13.7 (Varian medical Systems Pvt. Ltd., Palo Alto,
CA, USA), where CTV and PTV were contoured.
Plan was generated. Bone was shifted to Medical
Linear Accelerator Clinac DMX (Varian Medical
Systems Pvt.Ltd.,Palo Alto, CA, USA) treatment
couch ensuring proper immobilization. 2 D
treatment was planned. Plan was approved in two
parts of 25 Gy each since a single fraction plan of
50Gywas difcultto approve.Matchingwas seen
with beam light and source to surface distance
(SSD) was checked just like cobalt. The appropriate
eld size for radiation treatment was selected
making sure it covered the entire segment of bone.
A single fraction dose of 50 Gy using 6 MV photons
was delivered in two parts to the mid plane of bone
segment using a parallel-opposed anterio-posterior
andposterio-anteriorelds.Treatmenttimeforeach
part was 10minutes. Treatment was done on service
mode and not on routine mode. After completion
treatment delivery the bone segment was returned
to operation theatre maintaining proper chain of
aseptic precaution without any delay. The total time
required was almost 40 minutes in which radiation
delivery time was 20minutes and the rest of the 20
minutes in shifting of bone segment, imaging and
planning. Post ECI biopsy samples were taken
from various sites of the bone which turned out
negative for presence of malignancy (gure 6).
Post ECI the bone segment was pale and lost all its
tumourwhichpresentafterresection(gure7).The
bone was autoclaved and then re-implanted into
thebody. And postprocedure x-raydone. (gure
8) The patient started to weight bearing over her
lower limb with support on post procedure day 7
and there after ambulation with support began post
procedure day 15. Patient is on regular follow up
Jayeeta Sen, Amresh Kumar, Vividha Dubey et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
95
walking comfortably with support. Follow up to
continue every 3 monthly for two years.
Fig 1. Post Resection Femur with Residual Tumor
Fig 2. Post Fixation X-Ray
Fig 3. Layered Wrapping of Bone Segment for Radiation
Fig 4. Post ECI Bone Segment
Fig 5. Post ECI Biopsy Showing no Active Cells
Fig 6. Pre op CT scan
Extra Corporeal Irradiation to Treat Osteosarcoma at a Tertiary care
Institute in Central India: A Case Report
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
96
Fig 7. Histopathology
Fig 8. Pre Op X-ray Distal end Femur
Discussion
The entire appeal of multi-modality approach lies
in providing the best care utilising all the faculties
of oncology and to achieve the best outcome for the
patient. In MBT limb preservation could lead to a
better quality of life. One of the key requisites of
delivering ECI is the availability of all the modalities
at one institute. The need of proper operating
room, CT scanmachine for imaging, and the linear
accelerator to deliver radiation at one centre in
close proximity is of utmost importance since
time management is very crucial while executing
ECI. Limb salvage would result in better quality
of life and functional outcomes for the patient.
Limb reconstruction can be done using articial
prosthesis, allografts and autografts. Allografts
which are biologically reconstructed11 require
accesstolargebonebanksandtondamatching
bone donor and immunogenicity is difcult, and
also expensive. This also arises concerns regarding
the increased chances of transmission of infections
from allografts. So, the role of ECI hold simmense
importance in utilizing patients’ own bone segment
(autograft) as it provides a perfect anatomical
t, high dose of radiation ensures tumour kill,
convenient, cost effective and also minimizes
the risk of any disease transmission. Recycled
irradiated autograft was rst reported by Spira
and Lubin in 1968.12 Before re-implanting the bone
segment into body bone sterilisation is a must.
One of the advantages that we see with ECI is limb
function preservation which translates into weight
bearing and ambulation.In a study conducted
by Uyttendaele et,13 15 patients with primary
malignant bone tumours were treated with ECI
and they were followed up for 5 years and showed
excellent weight bearing. Similar studies were
conducted Hong et al,14 and Chen et al,15 exploring
the potential advantages of ECI and autograft
implantation. With ECI very high radiation dose
(50-300Gy) can be delivered. We delivered ECI
with 50Gy in a single fraction since previous
studieswhichstatesnoaddedbenetwithincrease
in dose and states chances of detrimental effect of
with higher doses of radiation.16,17,19 The advantages
with delivery of such high dose is the maximum
tumoricidal effect can be achieved which minimizes
the chances of local recurrence which was also
evident in a study conducted by Poffyn et al,18
where they had 0% recurrence post treatment with
ECI. And another study conducted by Davidson
et al19, with 50 patients where 4 patients had
recurrences. Most of the studies that we have been
conducted with ECI for MBT had a heterogenous
group of primary malignancy which makes it hard
to conclude if the recurrence was due to tumour
biology or due to failure of ECI.1,12,13, 14, 15,18 The dose
rate for ECI is still a matter of discussion and area
that needs to be explored. Though, with ECI we
can deliver doses without any radiation related
toxicity to the normal tissue since the bone has
been removed from the body. There is no chances
of unnecessary radiation exposure to surrounding
Jayeeta Sen, Amresh Kumar, Vividha Dubey et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
97
structures. In study conducted by Ahmad fauzi et
al20 comparing various methods of limb salvage ECI
was found to be good and convenient option. ECI
can only be executed successfully in patients where
biomechanical properties of the bone segment are
intact.
The potential benets of the procedure and a
few limitations faced during the procedure as
summarised in the table below:
Benefits Limitations
Higher local tumour control Single Plan approval could
not be done due to high
prescription dose.
Minimal chances of
recurrence Time is limiting factor since
the bone is to be irradiated
and transported back into the
OT within a limited interval.
No dose related normal tissue
toxicity Technically feasible set up
is needed to execute the
treatment.
Anatomically perfect fit with
autografts To draw conclusion between
local tumour control and
overall survival large scale
study with a higher sample
size needs to be done.
No requirement of finding
a matching donor bone and
immunogenicity
Chances of graft failure
No need to have an access to
bone banks Perioperative complication
Cost effective Delayed healing of wound.
Conclusion
ECI and autograft reconstruction procedures
for limb salvage are good, cost effective, and
convenient treatment option with good anatomical
and functional outcome. The relation between
overall survival and local tumour control needs to
be studied since most of the studies in literature
had a small sample size. Further studies with a
much larger patient cohort. The radiation delivery
requires prior preparation to be carried successfully
within limited time frame. This technique when
employed with proper selection of patient could
do wonders in regards to local control and post
procedure life style of patient.
References
1. Eyre R, Feltbower RG, Mubwandarikwa E, Eden
TO, McNally RJ. Epidemiology of bone tumours
in children and young adults. Pediatr Blood
Cancer 2009;53:941-52.
2. A.F. Kamal, H. Widyawarman, K. Husodo,
E.U. Hutagalung, W. RajabtoClinical outcome
and survival of osteosarcoma patients in
CiptoMangunkusumoHospital : limb salvage
surgery versus amputation Acta Med. Indones.,
48 (3) (2016), pp. 175-183
3. K. Ando, M.F. Heymann, V. Stresing, K. Mori,
F. Redini, D. HeymannCurrenttherapeu-tic
strategies and novel approaches in osteosarcoma
Cancers (Basel), 5 (2) (2013), pp. 591-616
4. A.K. Raymond, A.G. Ayala, S.
KnuutilaConventional osteosarcoma
5. C.D.M. Fletcher, K. Unni, F. Mertens (Eds.), World
Health Organization Classification of Tumors. Pa-
thology& Genetics Tumours of Soft Tissue and
Bone, IARC Press, Washington (2002), pp. 264-270
6. P.J. Messerschmitt, R.M. Garcia, F.W. AbdulKarim,
E.M. Greenfield, P.J. GettyOsteosarcomaJ. Am.
Acad. Orthop. Sur., 17 (8) (2009), pp. 515-527
7. Hong A, Stevens G, Stalley P, Pendlebury S, Ahern
V, Ralston A, et. al. Extracorporeal irradiation for
malignant bone tumors. Int J Radiat Oncol Biol
Phys. 2001;50:441–7.
8. Bohm P, Springfeld R, Springer H. Re-
implantation of autoclaved bone segments
in musculoskeletal tumor surgery. Clinical
experience in 9 patients followed for 1.1-8.4 years
and review of the literature. Arch Orthop Trauma
Surg. 1998;118:57–65.
9. Manabe J, Ahmed AR, Kawaguchi N, Matsumoto
S, Kuroda H. Pasteurized autologous bone graft
in surgery for bone and soft tissue sarcoma. Clin
OrthopRelat Res. 2004;258:66.
10. Anacak Y, Sabah D, Demirci S, Kamer S.
Intraoperative extracorporeal irradiation and re-
implantation of involved bone for the treatment
of musculoskeletal tumors. J Exp Clin Cancer Res.
2007;26:571–4.
11. Lu S, Wang J, Hu Y. Limb salvage in primary
malignant bone tumors by intraoperative
microwave heat treatment. Chin Med J (Engl)
1996;109:432–6.
12. D. Donati, C. Di Bella, T. Frisoni, L. Cevolani,
and H. DeGroot, “Alloprosthetic composite is a
suitable reconstruction after periacetabular tumor
resection,” Clinical Orthopaedics and Related
Research, vol. 469, no. 5, pp. 1450–1458, 2011.
13. E. Spira and E. Lubin, “Extracorporeal irradiation
of bone tumors. A preliminary report,” Israel
Journal of Medical Sciences, vol. 4, no. 5, pp.
1015–1019, 1968.
14. Uyttendaele D, De Schryver A, Claessens H, Roels
H, Berkvens P, Mondelaers W. Limb conservation
in primary bone tumours by resection,
extracorporeal irradiation and re-implantation.
J Bone Joint Surg Br. 1988 May;70(3):348-53. doi:
10.1302/0301-620X.70B3.3163694. PMID: 3163694.
Extra Corporeal Irradiation to Treat Osteosarcoma at a Tertiary care
Institute in Central India: A Case Report
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
98
15. Hong A, Stevens G, Stalley P, Pendlebury S, Ahern
V, Ralston A, et. al. Extracorporeal irradiation for
malignant bone tumors. Int J Radiat Oncol Biol
Phys 2001;50:441-7.
16. Chen WM, Chen TH, Huang CK, Chiang CC, Lo
WH. Treatment of malignant bone tumours by
extracorporeally irradiated autograft-prosthetic
composite arthroplasty. J Bone Joint Surg Br
2002;84:1156-61
17. Hong A, Stevens G, Stalley P, Pendlebury S, Ahern
V, Ralston A, et. al. Extracorporeal irradiation for
malignant bone tumors. Int J Radiat Oncol Biol
Phys. 2001;50:441–7.
18. Anacak Y, Sabah D, Demirci S, Kamer S.
Intraoperative extracorporeal irradiation and re-
implantation of involved bone for the treatment
of musculoskeletal tumors. J Exp Clin Cancer Res.
2007;26:571–4.
19. Poffyn B, Sys G, Mulliez A, Van Maele G, Van
Hoorebeke L, Forsyth R,et. al. Extracorporeally
irradiated autografts for the treatment of bone
tumours:Tips and tricks. Int Orthop2011;35:889-95.
20. Davidson AW, Hong A, McCarthy SW,
Stalley PD. En-bloc resection, extracorporeal
irradiation, and re-implantation in limb
salvage for bony malignancies. J Bone
Joint Surg Br. 2005 Jun;87(6):851-7. doi:
10.1302/0301-620X.87B6.15950. PMID: 15911672.
21. A.F. Kamal, A. Pitarini, Y. PrabowoMegaprosthesis
limb salvage surgery: outcome and challenges
in treating advanced bone tumour cases in vast
archipelago in Indonesia. A case series. Int J Surg
Open, 11 (2018), p. 30e36
Jayeeta Sen, Amresh Kumar, Vividha Dubey et. al.
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
99
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An Observational Study of Various Risk Factors, Clinical Presentation and Stage of
Carcinoma Breast, Correlation of Fine Needle Cytology / True Cut Biopsy with
Post Operative Histopathology Report, Staging and Management of
Carcinoma Breast 15
Aggressive Sebacous Carcinoma of Extremity : A Rare Case Report 85
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Glioblastoma Multiforme ( GBM) 73
Extra Corporeal Irradiation to treat Osteosarcoma at a tertiary care institute in
Central India: A case report 93
Functioning of Radiation Therapy During COVID-19 Pandemic in Red Zone COVID Hospital 35
Malignant Mixed Tumour Chondroid Syringoma of the Skin:
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Metastatic Breast Cancer to the Uterine Cervix Mimicking Cervical Cancer 49
Newer Treatment Options and Ongoing Research in Oncology 39
Primary Renal Ewing’s Sarcoma with Orbital Metastasis: A Rare Case Report 57
Role of Preoperative Ultrasound Guided Fine Needle Aspiration of
Axillary Lymph Nodes in Early Breast Cancer Patients 9
Surface Mould Brachytherapy Boost in Carcinoma Palate:
Challenges on the Road to a Better Therapeutic Ratio 23
Subject Index
Title Page No
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
104 Author Index
Name Page No Name Page No
Abhinav Choudhary 9
Akhilesh Patel 15
Aafreen Khan 23
Anand Lodhi 35
Amritjot Singh 49
Amritpal Singh Bhatia 49
Anil Sarolkar 53
Amresh Kumar 57
Ajaz A. Khan 73
Amresh Kumar 85
Amresh Kumar 93
Brajesh Gupta 45
Divya Krupa Muniyandi 39
Feroz Pasha 9
Ghanshyam Hatwar 45
Jayeeta Sen 29
Jayant Yadav 35
Jayeeta Sen 85
Jayeeta Sen 93
Karthikeyan Muniyandi 39
Mahendran C 23
M.Mohibul Haq 73
Mudasir A. Shah 73
Misba H Baba 73
Mohsin R Khan 73
Nayak B. Gull 73
Nazir A. Dar 73
Pravin Bhingare 45
Rajesh Sharma 15
Sujata Gupta 9
Sameer Kaul 9
Siddharth Gurwani 15
Sonam Wadhwani 15
Sunil Gurjar 15
Sneha Ninnama 15
Sahaj Palod 23
Sarolkar Anil 23
Saurabh Karnawat 35
Sanjay Dakhore 45
Sahaj Palod 53
Sajad A. Rather 73
Saurabh Karnawat 85
Saurabh Karnawat 93
Tauseef Ali 53
Taher Manaquibwala 57
Virendra Bhandari 23
Virendra Bhandari 29
Virendra Bhandari 35
Vivek Kanthed 53
Virendra Bhandari 53
Vividha Dubey 57
Virendra Bhandari 57
Virendra Bhandari 85
Vividha Dubey 85
Virendra Bhandari 93
Vividha Dubey 93
Yusuf Malik 29
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
105
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of the journal. There is no need to send printed
manuscript for articles submitted online.
Reprints
Journal provides no free printed, reprints,
however a author copy is sent to the main author
and additional copies are available on payment
(asktothejournalofce).
Copyrights
The whole of the literary matter in the journal is
copyright and cannot be reproduced without the
written permission.
Declaration
A declaration should be submitted stating that
the manuscript represents valid work and that
neither this manuscript nor one with substantially
similar content under the present authorship
has been published or is being considered for
publication elsewhere and the authorship of this
article will not be contested by any one whose
name(s) is/are not listed here, and that the order of
authorshipasplacedinthemanuscriptisnaland
accepted by the co-authors. Declarations should be
signed by all the authors in the order in which they
are mentioned in the original manuscript. Matters
appearing in the Journal are covered by copyright
but no objection will be made to their reproduction
provided permission is obtained from the Editor
prior to publication and due acknowledgment of
the source is made.
Guidelines for Authors
Indian Journal of Cancer Education and Research / Volume 8 Number 2 / July - December 2020
108
Approval of Ethics Committee
We need the Ethics committee approval letter
from an Institutional ethical committee (IEC) or
an institutional review board (IRB) to publish
your Research article or author should submit a
statement that the study does not require ethics
approval along with evidence. The evidence could
either be consent from patients is available and
there are no ethics issues in the paper or a letter
from an IRB stating that the study in question does
not require ethics approval.
Abbreviations
Standard abbreviations should be used and be
speltoutwhenrstusedinthetext.Abbreviations
should not be used in the title or abstract.
Checklist
• ManuscriptTitle
• Coveringletter:Signedbyallcontributors
• Previous publication/ presentations
mentioned, Source of funding mentioned
• Conictsofinterestdisclosed
Authors
• Middlenameinitialsprovided.
• Author for correspondence, with e-mail
address provided.
• Number of contributors restricted as per the
instructions.
• Identitynotrevealedinpaperexcepttitlepage
(e.g. name of the institute in Methods, citing
previous study as ‘our study’)
Presentation and Format
• Doublespacing
• Margins2.5cmfromallfoursides
• Titlepagecontainsallthedesiredinformation.
Running title provided (not more than 50
characters)
• Abstract page contains the full title of the
manuscript
• Abstract provided: Structured abstract
provided for an original article.
• Keywordsprovided(threeormore)
• Introductionof75-100words
• Headings in title case (not ALL CAPITALS).
References cited in square brackets
• Referencesaccordingtothejournal’sinstructions
Language and grammar
• UniformlyAmericanEnglish
• Abbreviations spelt out in full for the rst time.
Numerals from 1 to l0 spelt out
• Numerals at the beginning of the sentence spelt
out
Tables and gures
• Norepetitionofdataintablesandgraphsandin
text.
• Actual numbers from which graphs drawn,
provided.
• Figuresnecessaryandofgoodquality(color)
• Table and gure numbers in Arabic letters (not
Roman).
• Labels pasted on back of the photographs (no
names written)
• Figurelegendsprovided(notmorethan40words)
• Patients’ privacy maintained, (if not permission
taken)
• Creditnoteforborrowedgures/tablesprovided
• ManuscriptprovidedonaCDROM(withdouble
spacing)
Submitting the Manuscript
• Isthejournaleditor’scontactinformationcurrent?
• Isthe cover letter included with the manuscript?
Does the letter:
1. Include the author’s postal address, e-mail
address, telephone number, and fax number for
future correspondence?
2. State that the manuscript is original, not
previously published, and not under concurrent
consideration elsewhere?
3. Inform the journal editor of the existence of any
similar published manuscripts written by the
author?
4. Mention any supplemental material you are
submitting for the online version of your
article.Contributors’ Form(tobe modiedas
applicable and one signed copy attached with
the manuscript)
Guidelines for Authors
