Title: Scoliosis after resection of primary pediatric chest wall tumors

Authors:
Gehad Ahmed 1,2. Ihab M Emran 3,4. Ismail Rashad 4,. Mohamed S zaghloul5,6,. Mary Rabea Mahrous
7,8. Yomna AboTabl 9. Maged Elshafiey 2,10
1 General Surgery Department, Faculty of Medicine, Helwan University, Cairo, Egypt
2 Surgical Oncology Department, Children's Cancer Hospital 57357, Cairo, Egypt
3 Orthopedic Department, Faculty of Medicine ,Cairo University, Cairo, Egypt
4 Orthopedic department , Children's Cancer Hospital 57357, Cairo, Egypt
5 Radiotherapy Department, National Cancer Institute , Cairo University, Cairo,Egypt
6 Radiotherapy Department, Children's Cancer Hospital 57357, Cairo, Egypt
7 Radiology Department, National Heart Institute ,Giza ,Egypt
8 Radio-Diagnosis Department, Children's Cancer Hospital 57357, Cairo, Egypt
9Research Department , Children's Cancer Hospital 57357, Cairo, Egypt
10 Surgical Oncology Department , National Cancer Institute , Cairo University, Cairo,Egypt
Corresponding Author:
Gehad Ahmed , MD
Department of Surgery, Faculty of Medicine, Helwan University, Cairo, Egypt
Al Sikka Al Hadid Al Gharbeya, Helwan, Cairo
Postal code: 11795
E-mail: gehad.taha@gmail.com
ORCID ID: ORCID ID: https://orcid.org/0000-0002-8658-1525
- Telephone: 00201227268865
Declaration of interests: The authors declare there are no competing interests.
Funding: This research did not receive any specific grant from funding agencies in
the public, commercial, or not-for-profit sectors.
All work was done at Children's Cancer Hospital 57357, Cairo, Egypt

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 Scoliosis after resection of primary pediatric chest wall tumors
Abstract
Background: Scoliosis is one of the long-term consequences of surgical resection of pediatric chest wall
tumors. This study aimed to identify the risk factors associated with scoliosis development following the
resection of chest wall tumors.
Methods: Retrospective cohort study of 64 children who underwent resection of malignant chest wall
tumors from 2009 to 2022. univariate and multivariate analyses were used to investigate factors associated
with scoliosis development.
Results: The median age at the time of surgery was 7 years (range, 3–21), with 33 (51.6%) patients
undergoing surgery before the age of 10 years. The most common histology was Ewing sarcoma (n = 57).
A median of 3 (range, 1–5) contiguous ribs were resected. A total of 34 (53.1%) patients had anterior
CWTs and 30 (46.9%) had posterior CWTs. Concomitant partial lung and diaphragmatic resection were
performed in 12 patients ( lung, n=7; diaphragm, n=5). Scoliosis convex towards the resection side
developed in 21 (32.8%). The primary risk factors for scoliosis were resecting 3 or more ribs (OR 6.44)
and resection of the posterior rib segment (OR 5.49). Patients who had a tumor resection before 10 years
were not associated with a higher risk of scoliosis.
Conclusions: Scoliosis following resection of a primary malignant pediatric chest wall tumor is
associated with resection involving three or more ribs and resection of the posterior rib sector.
Key words: Scoliosis , Chest wall resection , Pediatric
Type of study; Retrospective observational
Level of evidence ;IV

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Introduction
Pediatric chest wall tumors (CWT) are rare, comprising 1.8% of all childhood cancers[1]. The Ewing
Sarcoma family is the most common malignant CWT, occurring most frequently during the second decade
of life[2] [3]. Treatment protocols of Ewing’s sarcoma include neoadjuvant chemotherapy followed by
surgery and/or irradiation [4][5][6][7]. Surgery aims to achieve a negative bone and soft tissue margin.
This usually entails the complete resection of the rib/s of origin ± a portion of the adjacent ribs. Possible
adverse outcomes of chest wall resection include scoliosis due to mechanical and neuromuscular
dysfunction [8][9]. While many studies focus on survival outcomes, few deal only with postoperative
scoliosis among pediatric population [10][11][12]. In addition, most reports are limited by small sample
size, and short follow-up time [13]. Therefore, counselling the patients and /or guardians on the expected
functional results after chest wall resection is one of the major challenges. This study will focus on the
factors associated with scoliosis development following the resection of primary malignant CWT in
pediatric and young adults.
Materials and Methods
This study was approved by the children’s cancer hospital 57357 (CCHE57357) Institutional review
board (No. 47/2023) , in accordance with declaration of Helsinki .After the approval was granted data
from all patients less than 21 years who had resection of primary malignant CWT between 2009 and 2022
were analysed retrospectively using electronic patient records. All patients had CT evaluation of the
primary tumor including precise tumor localization. Based on the level of involved ribs ,tumors were
classed in 2 groups : the upper ribs (1st–6th) and lower ribs (7th- -12th ). The rib segment involved by the
tumor was classified into 2 groups: anterior or posterior based the tangent line at the anterior edge of the
spinal body .Only patients who underwent follow-up review for at least 1 years after chest wall resection
at our center were included in the study. The following data were collected and analysied: Age at
diagnosis a, pathology, number of ribs involved, number of ribs resected, segment of rib resected, type of
reconstruction and incidence and degree of scoliosis as well as details follow-up review. Follow-up
duration was defined from chest wall resection to the last follow-up. Cobb angles was evaluated, by
spine surgeon and radiologist, during initial presentation and follow-up . Scoliosis was defined as a Cobb
angle greater than 10%. All patients were treated according to our hospital protocol which is based on
Children’s Oncology Group and included chemotherapy, tumor resection , and/or radiation therapy as
appropriate. Patients were followed up regularly according to the treatment protocol with CT scan at 6-
month and yearly after that . All patients and/or their guradian signed the informed consent before
treatment.
Statistical analysis

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Statistical analyses were performed using SPSS software, version 20 (SPSS Inc, Chicago, IL, USA).
Descriptive statistics are reported as number and percentage or median and range as appropriate.
univariate analysis was performed using Pearson chi-square test . A multivariate analysis with logistic
regression were used to investigate factors associated with scoliosis development . All analyses use two-
tailed tests and significance level was set at p < 0.05. Scoliosis development was The primary studied
event.

Results
During the study period, we identified 71 patients with CWT who were treated at our institution. A
total of 64 patients meet the inclusion criteria, these patients represent our final cohort for analysis.
Demographic information is presented in (Table 1). The median age at the time of surgery was 7 years
(range, 3–21), with 33 (51.6%) patients undergoing surgery before age 10. Thirty-five (54.7%) of the 64
children presented with a left-sided tumor. The most common histology was Ewing sarcoma (n = 57)
followed by osteosarcoma (n = 5). A median of 3 (range, 1–5) contiguous ribs were resected (one rib in 11
cases, two ribs in 17 cases, three ribs in 25 cases, four ribs in 8 cases, and five ribs in 3 case). The upper
(ribs 1–6), and lower (ribs 7–12) were resected in 28 (43.7%), and 36 (56.3%) patients, respectively. A
total of 34 (53%) patients had anterior CWTs and 30(47%) had posterior CWTs. Concomitant partial lung
and diaphragmatic resection were performed in 12 patients (lung, n=7; diaphragm, n=5). The vertebral
transverse processes were resected in one case. Surgical reconstruction included composite proline mesh
and methylmethacrylate , proline mesh and primary closure in:11(17.2%), 34 (53.1%), and 19 (29.7%)
of procedures, respectively. All defects were covered using either latissimus dorsi, serratus anterior or
pectoralis major advancement or rotational muscle flap.
There were no perioperative mortalities. Postoperative ventilation support were needed in 3 patients. The
resection margins were negative in 56 (87.5%) patients. Postoperative adjuvant radiotherapy to the tumor
site and ipsilateral chest was used in 41 patients, (45 Gy/25 (fx) over 5 weeks) . The median of follow-up
time was 8 years (range: 2 years to 13 years). During the follow-up period, 21 (32.8%) patients developed
scoliosis, all of them were towards the resection side (fig 1). The median Cobb angle was 26 (range, 7 to
51) (fig 2).Scoliosis developed at median of 2 years (range, 0.5 to 7) .Using univariate analysis , scoliosis
was associated with resection of ≥3 ribs (p = .033) and posterior segment resection (p = 0.008) . Age,
gender, level of resection and postoperative radiotherapy were not associated with the scoliosis. Using log
regression ,the odds of developing scoliosis after resection of posterior segment and resection of 3 or more
ribs were 5.49 and 6.44 respectively (table 2)

Discussion
The major goals of surgical management of CWT involve gross total resection and reconstruction to allow
for effective ventilation, protection of internal organs , providing for adequate lung and chest wall growth,
and avoid deformity . To achieve survival ,however some compromise is necessary as all of these
objectives can’t be met at the same time .[14] Scoliosis after resection of part of the chest wall is still one

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of the most common complications of treatment. The etiology of the scoliosis is multifactorial including
mechanical factors and neuromuscular dysfunction [15]. Although many factors ;age, number of ribs
resected and location of resection ,are anatomically and physiologically plausible to be associated with
scoliosis, it remains challenging to estimate them accurately. This may be due to the rarity of the disease
with a small sample size and short follow-up in most of the studies[13]. In the present study, we included
64 patients with median 7 years follow-up, 32.8% of patients (n=21) developed scoliosis during follow-up.
In a systematic review by theodorou and colleagues, the development of scoliosis was reported in 28
patients (28/126, 22.2%)[16] .The prevalence of scoliosis reported is lower than those noted in our
study .This could be partially explained by the limitation of this review in which scoliosis was not
reported in 33% of patients the median follow-up duration was 2 years , and thus scoliosis may have
developed later in some patients . This is supported by. Glotzbecker at al. [17], who reported development
of scoliosis in 11 patients (52%) among 21 patients followed for more than 10 years . In our cohort, new
onset scoliosis continued to develop 7 years after chest wall resection . Based on these findings scoliosis
surveillance should continue long-term after chest wall resection . In addition counselling the patients and
their families before chest wall resection about the risk of developing scoliosis . In concordance with
commonly observed characteristics reported that the convexity of the curve is always toward the side of
the resection[18]. In the present study the convex curves of scoliosis of all patients were toward the
resection side . This is explained by experimental animal studies in which intercostal nerve and rib
resection caused both mechanical and paralytic effect [19]. Our results goes in line with the previous
reports that have suggested that the age at the time of surgery is not associated with the development of
scoliosis [8][17] .We observe that patients less than 10 years did not significantly had higher incidence
of scoliosis (p =0.57). In the report by Scalabre et al. they categorize the age into 4 groups (<6,6-11,12-
15 and ≥15). They have concluded that patients in rapid growth period (<6,12-15)have significantly
higher incidence of scoliosis [9] . This is supported by previous studies which suggested young age as an
independent factor for the development of scoliosis. [9][20] These discipancies can by partially
explained by the different cutoff values used between studies .
Our results are consistent with other published reports and the recent systematic review who reported
the correlation of scoliosis development and the number of ribs resected and resection of posterior rib
element [9][16]. In the present study scoliosis development was significantly correlated with the number
of ribs resected(OR =5.49). Additionally in our study, posterior tumor position (OR= 6.44) was also
associated with the development of scoliosis . This is in agreement with published experimental work of
Langenskiöld, and Michelsson, who produced scoliosis in immature rabbits by posterior rib resection
[21]. Resection of the whole involved rib is based on the fact that ES may have skip lesions within the
marrow cavity . However, In anterior and lateral lesion preservation of the posterior segment is an option
. In this case ,skip lesions within the marrow should be excluded through a magnetic resonance imaging
or bone scan . Many other reports support our finding that the number of ribs resected is associated with
the development of scoliosis.[5, 10]. Even among the studies that did not report correlation between
number of ribs resected and the development of scoliosis, they advised for further investigation of this
factor as it approached significance[10].
Data regarding the correlation between resected rib location and scoliosis are inconsistent with mixed
results . Our findings are in line with saltsman and colleagues who demonstrates no correlation. Other

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investigators reported mixed results regarding which rib location is associated with scoliosis with some
demonstrate the correlation with upper ribs resection while others report the reverse [17][22].
Contrary to the previous opinion[1], the present study have reported that radiotherapy is not a risk
factor for scoliosis. This is supported by the luckas etal who reported no increased risk of scoliosis with
radiotherapy across the vertebral body [23] .Although Its clear from the present and previous studies that
most of the factors associated with scoliosis cannot be modified , the significance of this study is to
predict who will develop scoliosis . knowing this will allow us to tailor follow-up plans and provide
corrective surgery for those who are at high risk of scoliosis. We have the limitations related to
retrospective study design in addition scoliosis may be underestimated due to using supine scout CT for
analysis , compared to upright imaging .
Conclusions: Scoliosis following resection of a primary malignant pediatric chest wall tumor is
associated with resection involving three or more ribs and resection of the posterior rib sector.
Declarations
 Ethics approval and consent to participate. This study was approved by the children’s cancer
hospital 57357 (CCHE57357) Institutional review board (No. 47/2023) , in accordance with
declaration of Helsinki
 Consent for publication: Consent for publication was obtained from all participant and or their
legal guardian.
 Availability of data and materials: Data are presented in the study and any additional data are
available from the corresponding author upon request
 Competing interests: The authors declare there are no competing interests.
 Funding: This research did not receive any specific grant from funding agencies in
the public, commercial, or not-for-profit sectors
 Authors' contributions: GA,ME,IE put the concept and design.Data
acquision ;GA,ME,IE ,MZ,YA, IR, and MM.Analysis and data interpretation was done by
GA,IR,MM,MZ,IR,IE and MM.Drafting of the manuscript was done by GA,IE,ME ,MM ,IR and
All authors reviewed the manuscript

Legends for Figures

Fig 1A Coronal CT shows LT. sided osteosarcoma involving 5th -8th ribs
1B : Coronal CT View after resection of the 5th -8th ribs shows scoliosis towards the LT side (side of
resection )
Fig 2A: Coronal CT shows Ewing Sarcoma of the Rt 6th rib prechemotherapy

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 2B: Axial CT shows Ewing Sarcoma of the Rt 6th rib postchemotherapy
2C: Coronal CT shows scoliosis after resection of the 6th- and 7th ribs on the RT side

Legends for Tables

Table 1: Clinical and treatment Characteristics of the 64 patients with chest wall tumors
Table 2: Comparison between different variables that contribute to post-operative scoliosis :univariate
and log regression analysis

References
1. Shamberger RC, Grier HE (1994) Chest wall tumors in infants and children. Semin Pediatr Surg
3:267–76
2. Saenz NC, Hass DJ, Meyers P, et al (2000) Pediatric chest wall Ewing’s sarcoma. J Pediatr Surg
35:550–555. https://doi.org/10.1053/jpsu.2000.0350550
3. Mahesh Kumar AP, Green A, Smith JW, Pratt CB (1977) Combined therapy for malignant tumors
of the chest W all in children. J Pediatr Surg 12:991–999. https://doi.org/10.1016/0022-3468(77)90611-X
4. Kridis W Ben, Toumi N, Chaari H, et al (2017) A Review of Ewing Sarcoma Treatment: Is it Still
a Subject of Debate? Rev Recent Clin Trials 12:19–23.
https://doi.org/10.2174/1574887112666170120100147
5. (2012) Early diverting colostomy for perianal sepsis in children with acute leukemia. J Pediatr
Surg 47:e23–e27. https://doi.org/10.1016/J.JPEDSURG.2012.05.034
6. Ozaki T, Lindner N, Hoffmann C, et al (1995) Ewing’s sarcoma of the ribs. A report from the
Cooperative Ewing’s Sarcoma Study. Eur J Cancer 31:2284–2288. https://doi.org/10.1016/0959-
8049(95)00522-6
7. Athanassiadi K, Kalavrouziotis G, Rondogianni D, et al (2001) Primary chest wall tumors: early
and long-term results of surgical treatment. Eur J Cardiothorac Surg 19:589–93.
https://doi.org/10.1016/s1010-7940(01)00655-8
8. Lopez C, Correa A, Vaporciyan A, et al (2017) Outcomes of chest wall resections in pediatric
sarcoma patients. J Pediatr Surg 52:109–114. https://doi.org/10.1016/j.jpedsurg.2016.10.035
9. Scalabre A, Parot R, Hameury F, et al (2014) Prognostic Risk Factors for the Development of
Scoliosis After Chest Wall Resection for Malignant Tumors in Children. J Bone Jt Surg 96:e10.
https://doi.org/10.2106/JBJS.L.01535

7
10. Saltsman JA, Danzer E, Hammond WJ, et al (2021) Survival and Scoliosis Following Resection of
Chest Wall Tumors in Children and Adolescents. Ann Surg 274:e167–e173.
https://doi.org/10.1097/SLA.0000000000003495
11. Hayes-Jordan A, Stoner JA, Anderson JR, et al (2008) The impact of surgical excision in chest
wall rhabdomyosarcoma: a report from the Children’s Oncology Group. J Pediatr Surg 43:831–6.
https://doi.org/10.1016/j.jpedsurg.2007.12.021
12. Guillén G, García L, Marhuenda C, et al (2017) Thoracic wall reconstruction with bioabsorbable
plates in pediatric malignant thoracic wall tumors. J Pediatr Surg 52:377–381.
https://doi.org/10.1016/j.jpedsurg.2016.08.018
13. Incarbone M, Pastorino U (2001) Surgical treatment of chest wall tumors. World J Surg 25:218–
30. https://doi.org/10.1007/s002680020022
14. Grosfeld JL, Rescorla FJ, West KW, et al (1988) Chest wall resection and reconstruction for
malignant conditions in childhood. J Pediatr Surg 23:667–673. https://doi.org/10.1016/S0022-
3468(88)80642-0
15. Witte ZW, Mahoney JM, Harris JA, et al (2021) Biomechanical investigation of potential
prophylactic scoliosis treatments following various sizes of chest wall resection. Clin Biomech 87:105416.
https://doi.org/10.1016/j.clinbiomech.2021.105416
16. Theodorou CM, Lawrence YS, Brown EG (2023) Chest Wall Reconstruction in Pediatric Patients
with Chest Wall Tumors: A Systematic Review. J Pediatr Surg 58:1368–1374.
https://doi.org/10.1016/j.jpedsurg.2022.11.008
17. Glotzbecker MP, Gold M, Puder M, Hresko MT (2013) Scoliosis after chest wall resection. J Child
Orthop 7:301–307. https://doi.org/10.1007/s11832-013-0519-2
18. Kawakami N, Winter RB, Lonstein JE, Denis F (1994) Scoliosis Secondary to Rib Resection. J
Spinal Disord 7:522–7. https://doi.org/10.1097/00002517-199412000-00011
19. MacEwen GD (1973) Experimental Scoliosis. Clin Orthop Relat Res 93:69–74.
https://doi.org/10.1097/00003086-197306000-00009
20. Kawakami N, Winter RB, Lonstein JE, Denis F (1994) Scoliosis secondary to rib resection. J
Spinal Disord 7:522–7
21. Langenskiöld A, Michelsson J-E (1961) EXPERIMENTAL PROGRESSIVE SCOLIOSIS IN THE
RABBIT. J Bone Joint Surg Br 43-B:116–120. https://doi.org/10.1302/0301-620X.43B1.116
22. Soyer T, Karnak I, Ciftci AO, et al (2006) The results of surgical treatment of chest wall tumors in
childhood. Pediatr Surg Int 22:135–139. https://doi.org/10.1007/s00383-005-1537-z
23. Lucas JT, Fernandez-Pineda I, Tinkle CL, et al (2017) Late toxicity and outcomes following
radiation therapy for chest wall sarcomas in pediatric patients. Pract Radiat Oncol 7:411–417.
https://doi.org/10.1016/j.prro.2017.04.015

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