Scholars Journal of Medical Case Reports

Abbreviated Key Title: Sch J Med Case Rep

ISSN 2347-9507 (Print) | ISSN 2347-6559 (Online)
Journal homepage: https://saspublishers.com Radiotherapy

Radiotherapy’s Indications and Limits in the Management of Bone Ewing's

Sarcoma’s Children: About 22 Cases and Review of the Literature
R. Ousalm1*, O. El Kadiri1, D. Ait Antar1, M. Derfaoui1, A. El Omrani1, M. Khouchani1
1
Radiotherapy Department, Oncology and Hematology Hospital, Mohammed VI University Hospital, Marrakech, Morroco

DOI: 10.36347/sjmcr.2023.v11i06.012 | Received: 19.04.2023 | Accepted: 25.05.2023 | Published: 07.06.2023

*Corresponding author: R. Ousalm

Radiotherapy Department, Oncology and Hematology Hospital, Mohammed VI University Hospital, Marrakech, Morroco

Abstract Original Research Article

To study the indications and limits of radiotherapy in the treatment of bone Ewing's sarcoma’s children, we conducted
a retrospective study of 22 cases collected over a period of 10 years from January 2011 to December 2020. The study
took into account various clinical, radiological, therapeutic and evolutionary aspects of this pathology. The average
age of patients was 11 years, with gender equality. The diagnostic approach was identical, based on clinical,
radiological and histological data. Therapeutic management was based on chemotherapy, with local treatment
combining radiotherapy with or without surgical resection of the tumor. Ewing's sarcoma is a relatively rare malignant
tumor that grows mainly in bone and often has a large extension into soft tissue. All the bones of the skeleton can be
affected, with a clear predominance of the lower limb (60% of cases). Medical imaging is essential for diagnosis as
well as for therapeutic evaluation. While the diagnosis of certainty is currently based on histological and molecular
biology data. Therapeutic management combines a multimodal approach including chemotherapy, surgery and
radiotherapy. Nowadays the prognosis has improved thanks to the development of therapeutic methods.
Keywords: Ewing's sarcoma - radiotherapy - children - bone.
Copyright © 2023 The Author(s): This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International
License (CC BY-NC 4.0) which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original
author and source are credited.

charge in the radiotherapy department at the CHU

INTRODUCTION MOHAMED VI in Marrakech. The inclusion criteria
Ewing's sarcoma is a primary malignant bone used in our study are histologically confirmed bone
tumor, preferentially affecting children and adolescents, Ewing sarcoma and age less than or equal to 16 years at
and more rarely adults [1, 2]. It represents the the time of diagnosis. A pre-established exploitation
undifferentiated form of primary peripheral sheet was then filled in from the available information,
neuroectodermal tumors (PNET). It’s characterized by a the purpose of which is to specify for each location: the
chromosomal translocation t (11; 22) [1, 3]. Ewing's epidemiological characteristics of the patients, the
sarcoma is accompanied by extensive soft tissue diagnostic aspects, the therapeutic methods, as well as
extension, and all skeletal bones can be affected in the results of the treatment.
different proportions. Medical imaging plays a key role
in all stages of the management of bone Ewing's
sarcoma. While the certainty of the diagnosis is based RESULT
on histological examination. Its prognosis is classically The average age of the patients was 11 years,
poor because of the rapid appearance of metastases. The with extremes of 4 and 16 years and a sex ratio of 1.
radio sensitivity of Ewing's sarcomas has long placed
radiotherapy at the center of local treatment. However, For the background; 3 patients were from a 1st
its current therapeutic management is based on a degree consanguineous marriage, 2 had trauma to the
multimodal approach combining chemotherapy, surgery diseased limb, while one patient had exposure to
and radiotherapy. tobacco (passive smoking).

The time from onset of symptoms to diagnosis

MATERIALS AND METHOD ranged from 1 month to 1 year, with an average of 8
This work is part of a descriptive retrospective months. The delay was greater than or equal to 6
study carried out over a 10-year period between January months in 72% of cases.
2011 and December 2020. We collected 22 cases of
bone Ewing's sarcoma in children under 16 and took in
Citation: R. Ousalm, O. El Kadiri, D. Ait Antar, M. Derfaoui, A. El Omrani, M. Khouchani. Radiotherapy’s Indications
and Limits in the Management of Bone Ewing's Sarcoma’s Children: About 22 Cases and Review of the Literature. Sch J 1087
Med Case Rep, 2023 Jun 11(6): 1087-1099.
 R. Ousalm et al., Sch J Med Case Rep, Jun, 2023; 11(6): 1087-1099
The general condition of the patients was of cases; The topographical distribution is illustrated in
assessed according to the performance index of the figure 1. 3 patients had lymphadenopathy on initial
World Health Organization (WHO) [4]. 18% of cases clinical examination. Other clinical signs were present;
had WHO scale at 0; 72% had WHO scale at 1 and 9% 1 patient had fluid effusion syndrome on
had WHO scale at 2. The clinical signs were dominated pleuropulmonary examination, and 4 had cauda equine
by pain, found in 94.5% of cases and swelling in 85.5% syndrome on neurological examination.

Fig 1: Topographic distribution of the 22 cases

The para clinical assessment was based 45% of cases benefited from loco regional
essentially on radiological examinations. Standard X- computed tomography (CT). The results were in favor
ray data was available for 31.5% of patients. They were of osteolysis associated with soft tissue invasion in all
in favor of a poorly limited lacunar image associated patients. In addition, 30% of the examinations showed
with a periosteal reaction in the form of an onion bulb an image of osteocondensation with a rupture of the
and very significant thickening of the soft tissues. cortex in 20% of the cases.

Fig 2: CT of the pelvis in axial section product in a 9-years-old boy, which illustrates osteolysis with rupture of the
cortex of the right iliac wing associated with infiltration of the soft tissues

81% of cases benefited from loco regional equal to 10cm. None of the patients presented with
magnetic resonance imaging (MRI). These MRIs were invasion of the vascular axes. All the MRIs performed
able to show poorly circumscribed aggressive tumors of described a very significant infiltration of the soft
different sizes ranging from 4 to 18cm, with an average tissues and 22.5% had shown skip metastases.
of 11cm. 36% of cases had a tumor size greater than or

Fig 3: MRI of the pelvis in axial sections of the same patient figure 2 with injection of gadolinium and which
shows the significant infiltration of the soft tissues

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The definitive diagnosis is histological. All patients were classified as T3. Regarding lymph node
patients had a surgical biopsy. The pathological study involvement, 9% of cases were classified as N1. And
was in favor of malignant round cell tumor proliferation 22.5% of patients had pulmonary metastases classified
in all patients, with round nuclei in 63% of cases and as M1a, while 18% had distant bone metastases
scanty and dense cytoplasm in 90% of cases. The classified as M1b.
mitotic index was low in 90% of cases, tumor necrosis
was present in 72.7% of cases, vascular emboli were Therapeutic management includes systemic
found in 9% of cases, while perineural sheaths were treatment consisting of chemotherapy, local treatment
absent in all our patients. The immunohistochemical represented by surgery and radiotherapy.
study objectified the CD99 transmembrane glycoprotein
in all cases. None of the patients benefited from a All patients received primary chemotherapy
cytogenetic or molecular biology study. according to the Saint Jude Memphis protocol which
combines Cyclophosphamide and Doxorubicin.
All patients had an extension assessment.
Thoracic-abdominal and pelvic CT enabled the And All patients underwent post-
diagnosis of pulmonary metastases in 22.5% of cases, chemotherapy MRI evaluation; the tumor size regressed
inguinal lymphadenopathy in a patient with Ewing's partially in 58.5% of cases and completely in 4.5% of
sarcoma of the upper end of the femur, lumbo-aortic cases. Stabilization was noted in 13.5% of patients,
lymphadenopathy associated with while 22.5% of cases showed progression.
Ureterohydronephrosis (UHN) in a patient with Ewing's
sarcoma of the iliac wing. Bone scintigraphy was able 7 patients subsequently underwent surgical
to show bone metastases in 45% of patients. Of which treatment. A conservative treatment was performed in a
13.5% had distant bone metastases, 18% had spinal patient with Ewing's sarcoma of the lower femur, a
metastases in the form of metastatic skips and 9% had radical treatment was performed in three patients whose
both distant metastases and metastatic skips. disarticulation was recommended in a patient with
Myelograms and BOMs didn’t show any bone marrow Ewing's sarcoma of the iliac wing, an amputation
invasion. performed in a patient with Ewing's sarcoma of the
lower extremity of the femur and a parietectomy in a
For the classification of our patients, we used patient with Ewing's sarcoma of the rib. While
the TNM classification of the AJCC 8th edition for decompressive surgery was proposed in three patients
bone tumors [5]. 13.5% of cases were classified as T1; with vertebral Ewing's sarcoma. Lymph node dissection
58.5% of cases were classified as T2; while 27% of of the inguinal region was performed in a single patient.

Fig 4: Ewing's sarcoma of the right iliac wing in a 10-years-old girl, before chemotherapy (a) and after
neoadjuvant chemotherapy (b)

Our study focused on a series of 22 cases who 4.5% had a humeral location. In addition, 13.5% of our
all received radiotherapy. It was indicated for curative series had the indication of pulmonary irradiation. All
purposes in 45% of patients; Either alone for the patients obeyed a technical step. The preparation
unresectable tumors in 27% of cases or postoperatively phase of which is essential in order to choose a
for unsound margins in 18% of cases. It was indicated comfortable and reproducible position for the
for palliative or symptomatic purposes in 54% of cases, radiotherapy sessions. The use of restraints or sedation
in particular for analgesic purposes in 36% of cases and may be necessary to reproduce the same position. Then,
for decompressive purposes in 18% of cases. 59.5% of any patient scheduled for radiotherapy must perform a
the irradiated cases had tumors at the iliac level, 31.5% dosimetric scan which will serve as a support for virtual
had a femoral tumor, 22.5% had a vertebral tumor while treatment planning. It also makes it possible to better
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visualize the tumor and its extensions in the soft tissues using a fusion technique with CT or MRI images.

Fig 5: A fusion image in a 9-years-old child with right iliac Ewing's sarcoma

The dosimetric scanner makes it possible to 1233.500ml with an average of 470.510ml. While the
define the target tumor volumes. Three types of target PTVs varied from 238.476ml to 1764.794ml with an
volumes are to be defined. Macroscopic tumor volume average of 679.588ml.
(GTV) visualized by clinical and imaging data. The
microscopic tumor volume (CTV) corresponds to the The dosimetric scanner also makes it possible
microscopic extensions of the tumor. The predicted to define the organs at risk. They are delineated
tumor volume (PTV) obtained by adding a margin of 10 according to the irradiated area. It is all the healthy
to 15 mm around the CTV. In our series, the GTVs organs that surround the tumor. And this is a very
ranged from 40.15ml to 510.068ml with an average of important element to know in order to protect them and
246.978ml. The CTVs ranged from 122.141ml to document the dose received by each organ.

Fig 6: Contouring of a right iliac Ewing's sarcoma in a 9-years-old boy; GTV (red), CTV60 (pink), CTV45 (purple), PTV60
(blue), PTV45 (sky blue), organs at risk (bladder in yellow and intestines in sky blue)

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Fig 7: The dose received by the testicles of a 14-years-old boy with Ewing's sarcoma of the upper extremity of the left femur

The dose received by patients was 45Gy to with a daily fractionation of 1.5Gy. The duration of
66Gy in one to two so-called curative series in 90% of treatment varied from 12 days to 61 days with an
patients. While 9% received a palliative dose of 30Gy. average duration of 38 days.
13.5% of cases had lung metastases requiring 15Gy
lung irradiation. The dose overprint or the BOOST In order to correctly deliver the radiotherapy, a
represents the second series. In our study it is variable position control was done by portal imaging (PI) in all
from 5.4Gy to 21Gy. patients on the 1st, 2nd and 3rd day, then weekly and at
each change in the treatment plan. The occurrence of
The dose received was divided from 1.8Gy to acute toxicity and the proper course of the treatment
2Gy per fraction in 90% of cases. While 9% received were also checked during a weekly medical
palliative irradiation at 3 Gy per fraction. Patients consultation.
irradiated on pulmonary metastases received irradiation

Fig 8: Dosimetry of an Ewing sarcoma of the upper extremity of the femur in an 11-years-old boy with lung metastases

All patients underwent control MRIs after subsequently received a single cure according to the
radiotherapy. 23% of patients had a complete response VAI protocol which consisted of Vincristine, associated
to radiotherapy, 45% had a partial response, while 32% with Actinomycin, Ifosfamide with mesna, and only
had stability. 13.5% of cases continued with the VAC protocol which
consisted of Vincristine with Actinomycin and
In adjuvant, 40.5% of cases, having had a good Cyclophosphamide.
response, received chemotherapy according to the Saint
Jude Memphis protocol. 67.5% of cases received metronomic
chemotherapy at the end of treatment based on
40.5% who had a bad response received the Etoposide and Cyclophosphamide in combination with
VIDE protocol made of Vincristine associated with sodium valproate.
Ifosfamide, Doxorubicin and Etoposide. 27%
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The evolution was marked by a complete preferential involvement of subjects of Caucasian origin
remission in 13.5% of cases, a local recurrence in 18% (96% of cases) and the rarity of the involvement of
of cases, within a variable period of 12 to 36 months subjects of African, Afro-American and Asian origin
and an average of 27 months, a progression was noted (1.8 %) [3].
in 18% of cases 13.5% of which progressed remotely
with a variable delay of 2 to 8 months and an average of On the clinical level, the duration of the
4.5 months. In addition, we deplore the death of 27% of evolution of the disease before the diagnosis and the
cases with a delay of 1 month to 1 year and an average symptomatology are variable according to the
of 7 and a half months after radiotherapy. Whereas, aggressiveness of the tumor, the location without
22.5% of cases were lost sight of. forgetting the symptomatic treatments during the
medical consultations, without thinking of pushing the
investigations in order to have a diagnosis. Table 1
DISCUSSION shows the different topographic aspects described by
Ewing's sarcoma is an undifferentiated the IESS group (the intergroup Ewing's sarcoma study).
malignant tumoral proliferation originating in the bone Onset usually begins with localized pain and/or
and which was first described by James Ewing in 1921 swelling lasting a few weeks or months. The pain may
[3]. Before the age of 16, it’s the second most common be mild at first, worsened by exercise and become
malignant bone tumor (30% of cases) behind permanent even at night. A swelling is often present, a
osteosarcoma (60% of cases) [17]. Its incidence is source of pain sometimes associated with inflammatory
estimated at 3.2 per million children under 15 years old, signs. The notion of trauma, perhaps the initiating event
approximately 80 to 100 cases per year in France. In the that draws attention to the lesion, but also a reason for
United States, the incidence of Ewing's sarcomas hasn’t the delay in diagnosis. Certain modes of revelation may
changed for the past 30 years, remaining at 2.93 cases be specific to the location of the tumor, in particular
per million inhabitants [19]. Studies report frequencies spinal cord or radicular compression syndrome in spinal
of 9% in children under 5 years old, 60% are between 5 tumors, respiratory disorders and pleural effusion in rib
and 15 years old, 25% of cases are between 15 and 20 tumors, or even sphincter disorders in pelvic tumors [6].
years old and only 6% are over 20 years old [7]. Like As for lymphatic invasion, it is rare and is present in
osteosarcoma, the majority of epidemiological studies only 10% of cases [10]. General signs of disease
show a slight male predominance with a sex ratio of 1.5 progression, such as fever, fatigue, weight loss, or
to 2 [8, 9]. Despite advances in molecular biology and anemia, are present at diagnosis in approximately 10-
cytogenetics, the precise cause and risk factors for 20% of patients and should be investigated for
Ewing's sarcoma have not been identified. The presence disseminated disease or pelvic localization [11].
of a hereditary factor has been suggested given the

Table I: The different locations of Ewing's sarcoma on the skeleton in the IESS group [12]
Primary location Percentage %
Lower limbs 45,6
Femur 20,8
Fibula 12,2
Pelvis 20
Hipbone 12,5
Upper extremities 12,9
Humerus 10,6
Axial skeleton and ribs 12,9

The contribution of imaging is fundamental fusiform periosteal reaction in thin strips parallel to the
both for the diagnosis, the extension assessment, but long axis of the bone, producing an image in ―onion
also for the therapeutic evaluation and the detection of bulb‖. Bone lysis is poorly limited, irregular, giving a
recurrences during follow-up. The radiological worm-eaten appearance, with cortices appearing
appearance of Ewing's sarcoma is variable, but usually mottled, corresponding to the so-called permeation
associated with signs of osteolysis and sclerosis. The image. The existence of a Codman spur is inconstant,
typical form (which is not the most frequent), sitting on encountered in less than 30% of cases [3, 13, 14].
the long bones, is that of a lytic lesion, surrounded by a

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Fig 9: Radiographic presentation in three patients with Ewing's sarcoma: unilamellar periosteal apposition (a),
with permeative osteolysis (b), and osteolysis with Codman's spur (c) [3]

CT allows to objectify a periosteal reaction than conventional radiology would suggest. In T2, there
and a rupture of the cortex whereas MRI is effective for is a heterogeneous reinforcement of the tumor mass
the study of intramedullary involvement and soft tissues signal, and a usually intense contrast uptake after
[14]. In the thorax, CT is more interesting in rib lesions injection of gadolinium. T1 images, in high contrast
where it clearly shows bone lysis and the extent of soft with fat saturation, give very precise images of soft
tissue invasion, which contrasts with the pulmonary tissue involvement. The contrast between the
parenchyma [13]. In typical diaphyseal or metaphyseal- importance of the soft tissue mass visible on MRI and
diaphyseal forms, T1-weighted MRI shows sometimes discreet radiological involvement is quite
intramedullary damage that is often more significant characteristic of Ewing's sarcoma [3].

Fig 10: Ewing's sarcoma in an 8-year-old child, comparison of standard X-rays (a) and CT scans (b,c) [10]

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Fig 11: Ewing's sarcoma of the femur in a 9-years-old boy A. Plain X-ray appearance. B. Aspect in MRI imaging
showing the importance of intramedullary invasion and extension in the soft tissues [3]

The positive diagnosis is based on the remote dissemination, particularly in the bone and lung.
anatomo-pathological examination of a surgical biopsy The local therapeutic strategy depends on this
or trocar micro-biopsies. It must be sent fresh to the locoregional evaluation. MRI is the examination of
anatomo-pathology laboratory in order to allow the choice to analyze the local extension of a bone tumour.
molecular analyzes necessary for the diagnosis of The signal from the normal (fatty) medullary spaces
Ewing's sarcoma [15]. Macroscopically, the tumor has differs from that of the tumor so that it is possible to
irregular contours and very imprecise boundaries. It is a assess the extent of the tumor, to detect possible ―skip
greyish-white, soft, shiny mass, taking on a liquid, even metastases‖ and to evaluate a possible extension to the
milky consistency in the necrotic areas. tumor adjacent joint [6]. SAIFUDDIN reported, in his
Microscopically, the cells are all identical to each other, study of 26 cases, the presence of skip metastases in
rounded, measuring between 12 and 14µm. Their 25% of cases [11]. According to the Euro Ewing 99
nucleus, oval or rounded, is provided with a dense but protocol, in the event of a rib tumour, it’s essential to
dispersed chromatin and is delimited by a thin nuclear look for the existence of a pleural effusion, the nature of
membrane. Mitotic activity is highly variable, often which (tumor or reaction) will be sought by cytological
weak. The cytoplasms are pale and very sparse, with puncture. The presence of pleural effusion (even
fuzzy borders [3, 16]. Reorganizations are extremely positive) does not cause the patient to be considered as
frequent, linked to the fragility of the cells, associating metastatic but as a carrier of a locoregional disease. The
hemorrhage and necrosis. Immunohistochemistry remote extension assessment must systematically
allows positive diagnosis by demonstrating positive include a thoracic-abdominal and pelvic CT scan, a
staining for the CD99 glycoprotein (encoded by the bone scintigraphy and myelograms associated with an
MIC2 gene) overexpressed by cells of the Ewing tumor osteo-medullary biopsy. Metastases are common. They
family [17]. Its expression is not specific to Ewing are present in 20 to 30% of cases at the time of
sarcomas, it is also observed in a large number of diagnosis. These are mainly lung (38%) and bone
normal cells in the body, such as fibroblasts, as well as (48%) metastases. Other metastatic locations are rare
in various tumors such as certain carcinomas [20]. such as lymph node, brain and liver metastases 9% [3,
Demonstration of EWS gene rearrangements in 11, 21, 22]. The search for the 11-22 or 21-22 fusion
cytogenetics has become one of the essential elements transcript by reverse transcription polymerase chain
in the diagnosis of Ewing tumours. The t(11;22) reaction (RTPCR) on a pool of spinal taps confirms the
(q24;q12) translocation, first described, is present in 85 existence of micro metastatic diffusion, the prognostic
to 90% of cases, constituting a true cytogenetic marker value of which is now accepted [23]. The usefulness of
as well as the variant translocation t(21;22)(q22;q12) positron emission tomography (PET) or PET-CT in the
present in 5 to 10% of cases. There are other variants initial staging workup is unclear [24]. At least three
less frequently found [1, 11]. series note a better sensitivity of PET compared to bone
scintigraphy for the detection of bone metastases [25-
The aim of the extension assessment is to show 27]. However, since CT scans are generally limited to
the local extent of the tumour, its extension into the the neck above and the femurs below, not all bones are
bone and into the surrounding soft tissues, as well as the visualized as they would be with a bone scan knowing
involvement of the vasculo-nervous structures located the limitations of OS for osteolytic versus bone lesions.
nearby. It should also make it possible to judge the sclerotic nature. Moreover, PET can be more useful for
unifocal or multifocal nature of the lesions and their monitoring the response to chemotherapy and/or
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radiotherapy (in particular neoadjuvant chemotherapy),
in the postoperative evaluation of a possible recurrence, Radiotherapy can be delivered pre or
but also to guide the radiotherapist in defining his target postoperatively depending on the indications. However,
volumes to determine the dose needed to be the curative irradiation of a tumor requires high doses
administered. Currently, PET or PET/CT is increasingly and poses the problem of late toxicities in children.
used for the initial staging of patients with Ewing's Radiotherapy will be considered depending on the stage
sarcoma. National Comprehensive Cancer Network of the disease such as metastatic Ewing's sarcomas, seat
(NCCN) consensus guidelines recommend PET and/or of the tumor for certain inoperable tumor locations
bone scan for initial workup and baseline PET is either by their seats (spine and pelvis) or by their
recommended at COG (The Children's Oncology volumes or non-oncological surgery judged R1- R2 to
Group) referral if the primary bone tumor doesn’t fix on increase local control is to decrease the risk of
bone scintigraphy [28]. recurrence [31-33]. Patients must follow several steps
before starting treatment, including choosing a
The management of Ewing's sarcoma is comfortable and reproducible position using restraints
multimodal involving surgery, radiotherapy and and sedation, then performing a dosimetric scan or
chemotherapy. A common European protocol for the simulation. The fusion technique remains a crucial
treatment of Ewing's sarcomas and related tumors has element for the planning of ―dosimetry and quality
existed since 1999, but is still under evaluation. This control‖ radiotherapy. Advances in medical imaging
protocol, called Euro-EWING 99 for European Ewing and radiotherapy planning systems have greatly helped
tumor Working Initiative of National Groups 1999, the radiotherapy oncologist thanks to techniques such as
includes general treatment, chemotherapy and local the fusion of morphological images such as MRI, or
treatment, surgery and radiotherapy [3]. All the functional images such as PET scan performed before
decisions around the therapeutic strategy can only be systemic treatment (pre-chemotherapy tumor volume),
taken within the framework of a multidisciplinary or after (post-chemotherapy tumor volume) reflecting
consultation in a specialized center. The Euro-Ewing 93 the degree of response. The work of the radiotherapist
protocol includes, for localized forms, induction oncologist consists in defining the tumor volume to be
chemotherapy consisting of three to five initial courses, irradiated which corresponds to the initial or residual
called "Memphis", combining cyclophosphamide and tumor volume, called the macroscopic tumor volume
doxorubicin, and sometimes a combination of etoposide (GTV), to which a margin is added taking into account
and fosfamide. Maintenance chemotherapy after the possible microscopic extensions in different
surgery includes, depending on the response of the dimensions (CTV) taking into consideration the natural
tumour, first six courses of vincristine associated with history of the cancer, the areas of vulnerability to tumor
actinomycin D, then in a second phase, six courses of extension and anatomical barriers creating areas of
―Memphis‖ [4]. The Euro-Ewing 99 protocol includes resistance. A second margin is added to the CTV to
induction with six courses of vincristine, ifosfamide, correct any inaccuracies in the ―setup margin‖
doxorubicin and etoposide (VIDE). After surgery or positioning and the internal movements of the ―ITV‖
radiotherapy in non-surgical forms, chemotherapy then organs to obtain the final volume to be treated or
uses different drugs, either vincristine with actinomycin forecast volume (PTV) [34]. He must also outline
and ifosfamide (VAI), or vincristine, actinomycin and organs in anatomical relationship with the target
cyclophosphamide (VAC) [4]. In the forms of poor volumes to protect them from an excess of doses which
prognosis, the two protocols call for an intensification can compromise their function and consequently
of chemotherapy associating busulfan and melphalan permanent sequelae. The choice of organs at risk
inducing complete bone marrow aplasia [4]. The cure is mainly depends on the tumor location and largely
followed by an autologous bone marrow transplant determines the dose to be delivered, the ballistics and
taken by cytapheresis and frozen. the configuration of the beams. In the case of pelvic
involvement, it is essential to delineate the bladder,
Surgery is both a diagnostic and a therapeutic rectum, small intestine and femoral heads, which can
act. Its final goal is to carry out a carcinologically cause long-term disabling toxicity. Among the rules to
satisfactory intervention passing in all respects into follow when irradiating Ewing's sarcoma in a child:
healthy tissue without forgetting the possibility of avoid irradiating even partially the epiphyseal growth
conservation and construction. In the absence of plates in order to minimize the risk of member
contraindications, surgery can reduce the risk of local inequality. Circular radiation therapy should also be
recurrence, reduce radiation doses and analyze the avoided to reduce the risk of edema and compartment
histological response to chemotherapy. Historically, syndrome. The gonads must be excluded from the
surgery provides better loco regional control compared irradiation fields with additional protection (lead shells
to radiotherapy, but with advances in systemic for the testicles) to maintain fertility. Pay particular
treatments and irradiation techniques in the context of attention to the dose received by the soft tissues of the
multimodal treatment, local relapse rates have soles of the feet so as not to compromise the functional
decreased and the difference between the two means of result because walking imposes permanent constraints
local control has become almost insignificant [29, 30]. on this area. Achilles tendon radiation and nail roots
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should be excluded from the fields when possible. For discussed especially for head and neck tumors,
pelvic tumors, a full bladder can reduce the volume of especially in very young children. Intraoperative
irradiated small intestine while paying attention to the brachytherapy can be a good technique for irradiating
volume of the irradiated bladder because it is already certain locations [35]. If all the steps leading to the
weakened by Ifosfamide-based chemotherapy with the treatment are based on the availability of three-
risk of hemorrhagic cystitis. According to the Euro- dimensional images of the anatomical data and the
Ewing 99 protocol, the recommended dose is 44 to 54 target volumes, the verification of the positioning in the
Gy for operated patients. For non-operated patients, the absence of a "cone beam CT" in the treatment room,
recommended dose is 54 Gy, with overprinting up to 60 rested until now on the portal imagery "orthogonal
or 64 Gy depending on age and location [1]. According images" thanks to the visualization of the bony
to the MEMPHIS Protocol, the dose of irradiation structures. The correct positioning of the patient, of the
depends on the location of the tumour, and any prior Iso center of the beams and the limits of the fields are
excision of the tumour. If the resection was checked and controlled by carrying out control imaging
microscopically complete, the dose is 40 Grays. In the on the 1st, 2nd and 3rd day, then on a weekly basis, and
absence of surgery or in the case of incomplete each time the plan is modified of the treatment. The
resection, it is 60 grays for the limbs and depends on the most frequent acute complications of radiotherapy
neighboring organs for tumors located on the trunk mainly affect the skin (erythema, desquamation,
[11]. In the presence of risk factors for recurrence, an phlyctenes), the intestine and especially the rectum
additional dose may be administered at the level of the (radiation proctitis with pain, rectal bleeding, diarrhea),
tumor bed, ie in the region where the tumor was the urinary tract (radiation cystitis), the marrow spinal
removed for operated patients. This additional (myelitis, favored by local surgical or toxic trauma).
irradiation is called BOOST or overdose. It is facilitated Irradiation must also preserve the epiphyses in order to
by the placement by the surgeon of small radiopaque reduce the impact on growth in children, as well as the
clips at the level of doubtful areas of tumor residue femoral head, given the risk of epiphysiolysis of the
[35]. Radiation therapy is given 2 to 4 weeks after femoral head [6]. In the long term, the incidence of
surgery in case of conventional chemotherapy and 8 to radiation-induced sarcomas is approximately 5 to 35%,
10 weeks in case of high dose chemotherapy. Spreading 20 years after treatment for Ewing's sarcoma. These
and fractionation are generally standard, with a dose per radiation-induced secondary lesions can occur very late
fraction between 1.8 and 2 Gy, for 5 fractions per week. and their high incidence in Ewing's sarcoma appears to
In principle, patients receive 5 sessions per week from be partly related to associated chemotherapy (alkylating
Monday to Friday [1]. Other fractionations are possible agents) [37].
in the case of palliative radiotherapy 30Gy in 10
fractions, i.e. 3 Gy per fraction, or 5 fractions of 4Gy. Several studies have assessed the response to
For pulmonary radiotherapy, fractions of 1.5 Gy are radiation therapy compared to surgery. According to the
recommended to prevent radiation pneumonitis [35, study by SUDANESE–Institut RIZZOLI involved 196
36]. Three-dimensional conformal radiotherapy remains patients with no metastases at diagnosis. The age of the
the standard. However, intensity-modulated patients varies from 0 to 50 years old, of which 55%
radiotherapy (IMRT) often offers a ballistic advantage between 11 and 20 years old and 2% between 31 and 40
due to the complexity of the sites affected and the high years old. The results show an advantage to the use of
doses to be delivered. Proton therapy should be surgery associated with radiotherapy [30].

Fig 12: The retrospective role of surgery and radiotherapy according to the SUDANESE-Institut RIZZOLI study
[30]

© 2023 Scholars Journal of Medical Case Reports | Published by SAS Publishers, India 1096
 R. Ousalm et al., Sch J Med Case Rep, Jun, 2023; 11(6): 1087-1099
According to the CESS study, the use of years compared to 43% with the use of radiotherapy
surgery associated with radiotherapy with an absence of alone.
recurrence shows an advantage in 69% of cases at 3

Fig 13: Recurrence-free survival rate and failure according to local treatment [29]

Ewing's sarcoma is usually a rapidly growing inoperable tumors of small volume (<200ml) at least in
lesion. Locally it tends to invade the soft tissues, clinical and radiological partial response after initial
sometimes very significantly, and it can also extend to chemotherapy. The high-risk group includes tumors
the entire medullary cavity of the affected bone. This operated on after chemotherapy alone with ≥ 10%
invasion takes place through the Havers canals of the residual cells. Large inoperable tumors (≥200ml).
bone, then by a real infiltration of the surrounding Inoperable tumors of small volume (<200ml) and for
healthy tissues, contrary to what happens with which the initial chemotherapy only resulted in tumor
osteosarcoma where the tumor pushes back the healthy stability (response <50%). Tumors operated from the
soft parts by developing outside the limits of the outset large volume (> 200ml). But also tumors
initially affected bone. There are some cases when the operated after chemo and radiotherapy and small
tumor has, on the contrary, a rather slow evolution, volume < 200ml with > 10% perennial cells. The
remaining confined in the bone for a long time and not hypothesis of an infra-clinical dissemination of tumor
quickly giving metastases. This probably explains why cells explaining the appearance of metastases despite
the delay in diagnosis is not regularly found as a factor complete initial local control. Using the RT-PCR
of poor prognosis in clinical studies. The forms technique, West et al., detected occult tumor cells in
diagnosed late being perhaps the least aggressive. peripheral blood and bone marrow. It is currently
accepted that 20 to 40% of localized forms of Ewing's
The most important prognostic factor is the sarcoma have detectable tumor cells in the circulating
presence of metastases at diagnosis. The prognosis of blood by this method. Schleiermarcher et al., further
patients with isolated lung metastases is better than that showed that a positive RT-PCR in the bone marrow was
of patients with bone or bone marrow metastases. In strongly correlated with the existence of clinical
localized forms, the size of the tumor is found to be metastases (p = 0.0018). In this study, a positive RT-
prognostic in many studies, however since the PCR in the marrow of patients with apparently localized
increasingly frequent use of a surgical approach to these Ewing's sarcoma is a factor of poor prognosis. It will
tumours, the response to initial chemotherapy is found most likely be necessary to include the detection of the
to be very linked to the prognosis in the vast majority of fusion transcript in the bone marrow in future
cases. studies and eliminates the prognostic significance prospective studies [6].
of size for operated tumors [18]. The current European
protocol (Euro-Ewing 99) has stratified localized
tumors into several groups [19]: the standard risk group
CONCLUSION
represented by tumors operated on after chemotherapy Ewing's sarcoma remains a relatively rare
alone with <10% residual perennial cells. Tumors disease. It is a malignant tumor that frequently develops
operated on from the outset of small volume (<200ml). in bone tissue and rarely in soft tissue. It is a pathology
Tumors operated after chemo and radiotherapy and of of the child in its osseous localization and of the young
small volume with < 10% of residual cells. As well as adult in its extra osseous localization. Its diagnosis is
© 2023 Scholars Journal of Medical Case Reports | Published by SAS Publishers, India 1097
 R. Ousalm et al., Sch J Med Case Rep, Jun, 2023; 11(6): 1087-1099
currently based on histology and molecular biology 9. Indelicato, D. J., Keole, S. R., Lagmay, J. P.,
data. It is necessary to make an early diagnosis before Morris, C. G., Gibbs Jr, C. P., Scarborough, M. T.,
the metastatic stage and to institute an adequate ... & Marcus Jr, R. B. (2011). Chest wall Ewing
treatment in order to improve the prognosis of the sarcoma family of tumors: long-term
disease. Its prognosis has been significantly improved outcomes. International Journal of Radiation
thanks to modern therapies. The management of Oncology* Biology* Physics, 81(1), 158-166.
Ewing's sarcoma is multidisciplinary based on the doi:10.1016/j.ijrobp.2010.04.066
combination of surgery, radiotherapy and 10. Ayadi, L., Chaari, C., Kallel, R., Ayadi, K., Khabir,
chemotherapy. Radiotherapy still has very specific A., Jlidi, R., ... & Sellami-Boudawara, T. (2010).
indications despite the development of surgical Sarcome d'Ewing Osseux et Extra Osseux: Etude
techniques and chemotherapy protocols. The aim of anatomo-clinique de 29 cas. Tunisie
current treatments is to reduce the sequelae directly médicale, 88(5), 301-305.
linked to therapies in the so-called good prognosis 11. Elghazi, T. (2011). Le sarcome d’Ewing costal
forms and to improve the results of the treatment of the chez l’enfant (à propos de 8 cas). Thèse Méd.
so-called poor prognosis forms, whose survival rates Rabat, N°83.
currently remain disappointing. Many patients, 12. Kissane, J. M., Askin, F. B., Foulkes, M., Stratton,
however, still die from the progression of their tumor. L. B., & Shirley, S. F. (1983). Ewing's sarcoma of
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