Extra corporeal Irradiation and Surgical Reinforcement in Primary Malignant Bone tumors: A tertiary cancer center experience as a “A Poor man’s Biological Prosthesis”

Abstract

Limb preserving surgeries are established as oncologically safe and standard of care in the management of primary malignant bone tumors. Surgical resection, extracorporeal irradiation and surgical reimplatation is one among the limb sparing techniques. In our institute, we adopted this method in 9 patients and analysed their oncological outcome.Materials and Methods: Between 2019 to 2022 Nine patients diagnosed with primary bone tumors after appropriate neoadjuvant chemotherapy, underwent surgical resection and extracorporeal irradiation and surgical fixation. 6 were men and 3 women. 6 patients were diagnosed with ewing's sarcoma and three with Osteogenic sarcoma. The median age was 14years (range 8-20 years). The treated bones were femur (n=4), tibia (n=2), humerus (n=2), iliac bone with acetabulum (n=1). After informed consent and appropriate investigations, patients underwent wide local excision. The resected bone was irradiated with single dose of 50Gy, re-implanted and stabilised with screws and plates. Patients were mobilised with appropriate mechanical aids and referred for completion of chemotherapy. All were followed-up with appropriate imaging.

Full text

Draft copy of article for RJMS
Research Journal of
Medical Science
Research Article doi:
Extra corporeal Irradiation and Surgical
Reinforcement in Primary Malignant Bone tumors:
A tertiary cancer center experience as a “A Poor
man’s Biological Prosthesis”
1
Naveen.T,
2
Manjula MV,
3
Pawar YS,
4
Tanveer.P,
5
Sridhar P,
6
Ganesh KM,
7
Varatharaj C,
8
Rekha Reddy B,
9
Shwetha B,
10
Mageshraja Kannan,
11
Ravi Arjunan,
1
Professor, Department of Radiation Oncology, Kidwai Memorial
Institute of Oncology, Hosur Road, Bangalore 560029, India.
2
Assistant Professor, Department of Radiation Oncology, Kidwai
Memorial Institute of Oncology, Hosur Road, Bangalore 560029, India.
3
Assistant Professor, Department of Radiation Oncology, Kidwai
Memorial Institute of Oncology, Hosur Road, Bangalore 560029, India.
4
Professor, Department of Radiation Oncology, Kidwai Memorial
Institute of Oncology, Hosur Road, Bangalore 560029, India.
5
Associate Professor, Department of Radiation Oncology, Kidwai
Memorial Institute of Oncology, Hosur Road, Bangalore 560029, India.
6
Professor, Department of Radiation physics, Kidwai Memorial Institute
of Oncology, Hosur Road, Bangalore 560029, India.
7
Associate professor
Medical Physicist, Department of Radiation Physics,
Kidwai Memorial Institute of Oncology, Hosur Road, Bangalore 560029,
India.
8
Medical Physicist, Department of Radiation Physics, Kidwai Memorial
Institute of Oncology, Hosur Road, Bangalore 560029, India.
9
Associate professor
Medical Physicist, Department of Radiation Physics,
Kidwai Memorial Institute of Oncology, Hosur Road, Bangalore 560029,
India.
10
Medical Physicist, Department of Radiation Physics,Kidwai Memorial
Institute of Oncology, Hosur Road, Bangalore 560029, India.
11
Professor, Dept of Surgical Oncology MS,Kidwai Memorial Institute Of
Oncology, Hosur Road, Bangalore 560029, India.
OPENACCESS
Keyword
Primary bone tumours,
extracorporeal irradiation, Organ
preservation, biological prosthesis.
Corresponding Author
Dr Pawar. Y.S,
Assistant Professor,
Department of Radiation Oncology
Kidwai Memorial Institute of Oncology
Hosur Road, Bangalore 560029, India.

Draft copy of article for RJMS
Received:9 May 2023
Accepted:16 June 2023
Published:28 July 2023
Citation:
CopyRight: MAK HILL Publications
ABSTRACT
Limb preserving surgeries are established as oncologically safe and
standard of care in the management of primary malignant bone tumors.
Surgical resection, extracorporeal irradiation and surgical reimplatation is
one among the limb sparing techniques. In our institute, we adopted this
method in 9 patients and analysed their oncological outcome.Materials
and Methods: Between 2019 to 2022 Nine patients diagnosed with
primary bone tumors after appropriate neoadjuvant chemotherapy,
underwent surgical resection and extracorporeal irradiation and surgical
fixation. 6 were men and 3 women. 6 patients were diagnosed with
ewing’s sarcoma and three with Osteogenic sarcoma. The median age
was 14years (range 8-20 years). The treated bones were femur (n=4), tibia
(n=2), humerus (n=2), iliac bone with acetabulum (n=1). After informed
consent and appropriate investigations, patients underwent wide local
excision. The resected bone was irradiated with single dose of 50Gy, re-
implanted and stabilised with screws and plates. Patients were mobilised
with appropriate mechanical aids and referred for completion of
chemotherapy. All were followed-up with appropriate imaging. Out of the
9 patients, 1 patient with osteosarcoma after six month of disease free
interval developed local recurrence along with distant metastasis. One
patient with Ewing’s sarcoma had non-union, however the patient was
still on adjuvant chemotherapy. The remaining seven patients remained
disease free till the last follow-up. The mean musculoskeletal tumour
society scoring system (MSTSS) was 3 (range 1-4).Conclusion: In
government aided centres where majority of patients belong to lower
socio-economic class, unsupported by health insurance, limb preservation
by extracorporeal irradiation can be an alternative modality. ECRT would
serve as best size matched, “poormans” biological prosthesis, which is
less expensive, readily available and yet maintaining the purpose of limb
function.

INTRODUCTION
Primary bone tumors, commonly seen in
children and adolescents are rare accounting to
approximately 0.5 percent of all cancers in the
world.
[1]
In India, according to Bombay cancer
registry, bone malignancies were found to
represent 0.9% of all cancers and Ewing sarcoma
being commonest.
[2]
In Karnataka, a retrospective
data of 523 bone tumours, collected over 36 years,
Osteogenic sarcomas were 45.7% and 19.4% were
Ewing’s sarcoma.
[3]
The difference in incidence is
due to its rarity.
Historically, limb deforming surgery was
the standard of care. Since 1960, with the
involvement of inter-disciplinary team in decision
making, technological advances in radiation
oncology, radiology and newer chemotherapeutic
drugs, treatment concept has translated from
deforming surgery to limb sparing and function
preservation methods. Although, limb
preservation using mega prosthesisis is commonly
practiced, but the associated complications like
loosening of implant, implant failure, infection,
heaviness of the limb, and cost of the implant are
the inevitable sequel. The other methods of limb
preservation are adopting biological
reconstruction methods.
Re-implantation of devitalised or tumour
sterilized bone segment is one of the alternative
reconstruction option. The various methods of
sterilizing the tumours are autoclave, microwave,
pasteurization, liquid nitrogen, and radiotherapy
(extracorporeal radiotherapy).
[4-9]
The advantage of
extracorporeal radiation and re-implantation is
being cost effective, convenient yet maintaining
the objective of limb preservation. Although the
technique was first adopted by Spiraet al in 1968
however it was not in regular practice due to lack
technical expertise.
[10]
We are reporting our initial
experience and preliminary results of nine patients
treated with ECR.
MATERIALS AND METHODS
From 2019 to 2022, nine patients with
histologically proven primary malignant bone
tumours were enrolled after obtaining approval
from institutional ethical review board. All patients
were evaluated in multidisciplinary clinic involving
orthopaediconco-surgeons, radiation oncologists
and medical oncologists. Patients were evaluated
with complete hemogram, liver and renal function
tests. Magnetic resonance imaging (MRI) was
performed in all the patients to measure precise
extension of the tumour, its relation to neuro-
vascular bundle, presence of extra osseous
component, involvement of bone marrow and to
assess the cortical strength. Computed
tomography of thorax and bone scan was done to
rule out distant metastasis. PET CT scan was done
when ever feasible and required. Patients with
Ewing’s sarcoma family of tumours underwent
bone marrow evaluation as a part metastatic
workup. Patients with pathological fracture or
compromised bone strength were excluded for
ECRT.
Surgery
The surgery was planned 4 weeks after
appropriate neoadjuvant chemotherapy (NACT).
Adhering to the oncological principles, en-block
resection of the tumour with adequate margins
was done. The adequacy of the margins was
confirmed by frozen section taken from multiple
sites. The resected bone segment was given
thorough antibiotic wash before it is draped and
packed in sterile plastic bags. Adequate measures
were taken to avoid any air pockets while packing
before sending for irradiation.
Extra-Corporeal Radiation (ECRT)
A dedicated linear accelerator was kept
ready, to receive the specimen and execute
radiation treatment under aseptic precautions.
The specimen received from OT was placed in a
water phantom, customised as an irradiator. The
phantom was filled with sterile, distilled water
used routinely for RFA measurements (figure1).
The radiation was delivered using 6MV photons, at
maximum dose rate, with parallel opposing beam
arrangements. The radiation dose of 50Gy in single
fraction at mid plane was prescribed. Based on
field dimensions and separation, treatment
monitor units (MU) were calculated by tissue
maximum ratio formula. The radiation was
delivered by isocentric (SAD) technique to reduce
the treatment time. The turnaround time of
radiation ranged between 20-25mins. The bone
segment thus irradiated was sent back to OT under
aseptic precautions for surgical re-implantation
and fixation using plates and screws (figure 2 & 3).
Figure 1: ECRT set-u p with a water phantom c ustomised as bone
irradiator

Figure: 2 & 3: Post operative images of b one segment fixed using nails
and screws
RESULTS
Between Aug 2019 to Dec 2021, Nine patients
diagnosed with primary malignant bone tumours
were included in this series. Six patients were
diagnosed with Ewing’s sarcoma and three
patients with osteosarcoma. All patients
underwent wide local excision, extra-corporal
bone radiation (ECI) and re-implantation of the
devitalised bone segment and stabilised with
plates and screws. All patients had R0 resection.
The patient demographic details and characteristic
features of the disease is mentioned in Table 1.
Among the nine patients, six were male and three
were female. The median age was 14 years (8years
– 20 years). Among the nine patients, six patients
were diagnosed with Ewing’s sarcoma and three
with Osteosarcoma. The treated bones were
femur (n=4), tibia (n=2), humerus (n=2), iliac bone
with acetabulum (n=1). The radiation dose
delivered was 50Gy in single fraction at midplane.
The median turnaround time of radiation delivery
(from the time of specimen reaching treatment
room to operating theatre) was 12 minutes (9-
25minutes).
Patients were permitted to mobilize under
supervision with appropriate mechanical
assistance. Patients with lower extremity disease,
partial guarded weight bearing, walker assisted
movement was permitted. Gradual complete
weight bearing walking was allowed once the
union was confirmed radiologically and as advised
by the surgeon. After wound healing and
appropriate postoperative rehabilitation, patients
were further referred for completion of adjuvant
treatment if any and kept on regular follow-up.
Out of the nine patients, one patient having
osteosarcoma developed local recurrence along
with distant metastasis after six months of disease
free interval. One patient with Ewing’s sarcoma
had non-union however the patient was still on
adjuvant chemotherapy. The remaining seven
patient remained disease free till the last follow-
up. Using modified musculoskeletal tumour society
scoring system (MSTSS) the mean score was 3
(range 1-4)
Table 1: Patients demographics (n=9)
Sl
No
Age
(yrs)
Sex Histology Primary Site Radiation Dose Local D isease
statue
Distant
Metastasis
Local
Complications
1 20 M ES Femur 50 Gy NED NO NIL
2 20 F OS Femur 50Gy NED NO NIL
3 19 M ES Ilium 50Gy NED NO NIL
4
14
F
ES
Tibia
50Gy
NED
NO
NIL
5 10 M ES NO NIL
6 11 M OS Tibia 50Gy Recurrence Lung Metastasis
on metronomic
chemotherapy
--
7 8 F ES Humerus 50Gy Pathological
Fracture/ No n
union
On
Adjuvant chemotherapy
--
8 10 M ES Tibia 50Fy NED NO NIL
9 17 M OS Radius 50Gy NED NO NIL
M=Male,F=Female,ES=Ewings’sarcoma,OS=Osteogenicsarcoma,NED=No evidence of disease.
DISCUSSION
The concept of organ preservation and
function restoration with optimum quality of life
has resulted in paradigm shift in the management
of malignant bone tumours from amputation to
limb preservation. ECI and reimplantation is one
among the limb preservation techniques. This
technique was first described by Spirit et al in
1968, followed by few series.
[11-17]
The radiobiological advantage of this
method is that, the diseased segment of bone is
removed out of the body and irradiated to very
high doses with no dose to normal structures. The
radiation dose delivered in the range of 50-300Gy
is ablative and tumouricidal, with no dose to the
surrounding normal tissues and thereby achieving
maximum therapeutic gain.
The biological advantage of ECI is that, it
is one of the best anatomically size-matched bone
grafts for reconstruction. This procedure is cost-
effective also provides psychological support to

the patients that their own bone is being used as
prosthesis.
The graft infection and failure rates were
similar to any other grafts. The risk of wound
infection documented in a case series is
approximately 17 %.[12,16]In our study, none of the
patients had wound site infection. As the wound
Infection can result in delayed healing, delayed
union or non-union, even the failure of graft,
consequentially causing delay in adjuvant
chemotherapy, therefore meticulous aseptic
precautions should be practiced at all the steps.
We preferred to restrict our radiation
doses to 50Gy, as the doses beyond 50Gy is not
required to sterilise the tumour, also higher doses
are associated with possible detrimental effects
such as delayed revascularisation, reduction in
bone strength, delayed union and bone
incorporation of the graft.[10,13,18,19]
Local recurrence has been rarely reported
after extracorporeal irradiation.[20] In our study one
patient with osteosarcoma had local recurrence
along with multiple distant metastases.
The mean revised Musculoskeletal
Tumour Society Score was 3 (1-4) in our study,
which was comparable with other series.
The potential drawback of extracorporeal
irradiation is the lack of information of tumour
response to the chemotherapy and adequacy of
the margins which are both predictive and
prognostic factors.
CONCLUSION
In our institute we adopted ECRT as one
of the option of limb preserving method as it
would serve as best size matched, “poormans”
biological prosthesis, which is less expensive,
readily available and yet maintaining the purpose
of limb function.
REFERENCES
1. Karun Jain 1, Sunila, R
Ravishankar, Mruthyunjaya et al. Bone tumors
in a tertiary care hospital of south India: A
review 117 cases. Indian J Med
PaediatrOncol2011;32:82-85.
2. Yeole BB, Jussawalla DJ. Descriptive
epidemiology of bone cancer in greater
Bombay. Indian J Cancer 1998;35:101-106
3. Rao VS, Pai MR, Rao RC, Adhikary MM.
Incidence of primary bone tumours and
tumour like lesions in and around Dakshina
Kannada district of Karnataka. J Indian Med
Assoc 1996;94:103-104, 121
4. Hurson BJ (1995) Limb-sparing surgery for
patients with sarcomas [editorial]. J Bone Joint
Surg Br 77:173–17.
5. Hong A, Stevens G, Stalley P, Pendlebury S,
Ahern V, Ralston A, et al. Extracorporeal
irradiation for malignant bone tumors. Int J
RadiatOncolBiolPhys2001;50:441-7.
6. 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.
7. Manabe J, Ahmed AR, Kawaguchi N,
Matsumoto S, Kuroda H. Pasteurized
autologous bone graft in surgery for bone and
soft tissue sarcoma. ClinOrthopRelat Res
2004;258-66.
8. Anacak Y, Sabah D, Demirci S, Kamer S.
Intraoperative extracorporeal irradiation and
re-implantation of involved bone for the
treatment of musculoskeletal tumors. J
ExpClin Cancer Res 2007;26:571-4. 14. Lu S,
9. 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
10. Spira E, Lubin E. Extracorporeal irradiation of
bone tumors. A preliminary report.Isr J Med
Sci 1968;4:1015-9.
11. 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;70:348-53.
12. Araki N, Myoui A, Kuratsu S, Hashimoto N,
Inoue T, Kudawara I, et al. Intraoperative
extracorporeal autogenous irradiated bone
grafts in tumor surgery. ClinOrthopRelat Res
1999 Nov;368:196-206.
13. Hong A, Stevens G, Stalley P, Pendlebury S,
Ahern V, Ralston A, et al. Extracorporeal
irradiation for malignant bone tumors. Int J
RadiatOncolBiolPhys2001;50:441-7.
14. 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.
15. 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;87:851-7.
16. Puri A, Gulia A, Agarwal M, Jambhekar N,
Laskar S. Extracorporeal irradiated tumor
bone: A reconstruction option in diaphyseal

Ewing’s sarcomas. Indian J
Orthop2010;44:390-6.
17. 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.
IntOrthop2011;35:889-95.
18. 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;87:851-7.
19. Currey JD, Foreman J, Laketic I, Mitchell J,
Pegg DE, Reilly GC. Effects of ionizing radiation
on the mechanical properties of human bone.
J Orthop Res 1997;15:111-7.
20. Chen TH, Chen WM, Huang CK. Reconstruction
after intercalary resection of malignant bone
tumours: Comparison between segmental
allograft and extracorporeally-irradiated
autograft. J Bone Joint Surg Br 2005;87:704-9.