Assessment of local complications with preoperative versus postoperative radiotherapy in patients with soft tissue sarcoma in extremities: A randomized comparative clinical trial

Abstract

Background

Radiotherapy is considered a cornerstone as adjuvant or neo adjuvant to surgery in extremity soft tissue sarcoma (ESTS). Wound complications are the most agonizing complication that may have an impact on patient's functional outcome following radiotherapy. The best care for ESTS is by combining extensive surgical excision with safety margin and radiotherapy either preoperative (neoadjuvant) or postoperative. Preoperative radiotherapy allows for lower dose of radiation over smaller fields which is supposed to decrease long-term complications. However, several studies have shown that early complications which include wound dehiscence, infection, seroma and burn may be more frequent with preoperative radiotherapy than with postoperative radiotherapy. Most of these studies were retrospective. This study aims to prospectively assess and compare the early complications associated with radiotherapy in both techniques.

Hypothesis

Preoperative radiotherapy is not inferior to postoperative radiotherapy regarding early wound complications.

Patients and methods

Between January 2021 and June 2022, we prospectively studied 22 patients and categorized them into two groups, group A (preoperative radiotherapy) and group B (postoperative radiotherapy). We included patients with extremity soft tissue sarcoma in skeletally mature patients who were randomized into two groups with follow up 9–12 months. Wound complications, local complications, recurrence, time for wound healing and survival rate were recorded and analyzed using SPSS 25.

Results

22 patients were included, 10 in group A and 12 in group B, their mean age was 46.4 years with mean follow up 9 months. The major wound complications were higher in group A (preoperative radiotherapy). in comparison with group B (postoperative radiotherapy), however, this was not statistically significant. While other local complications were higher in group B, it was also statistically insignificant. Time for wound healing was higher in group A more than group B and was statistically significant (p value = 0.011)

Conclusion

No increase in the wound complications rate with preoperative radiotherapy by using low fractionated doses of radiotherapy and increasing interval before surgery to six weeks, although there is increased risk of delayed wound healing time after surgery. The size and site of the tumor may increase the risk of wound complications unrelated to the type of radiotherapy.

Level of evidence

II: clinical trial.

1. Introduction

Sarcomas are rare tumors arising from mesenchymal tissue. Extremity Soft tissue sarcomas (ESTS) comprise less than 1% of malignant cancers.^1,2 ESTS are malignant tumors which arise in upper and lower extremities from mesenchymal tissues including synovium, muscles, fat, subcutaneous tissue and skin² Malignant peripheral nerve sheath tumors (MPNST) are also included Although ectodermal in origin, although ectodermal in origin, because of the similarities in clinical features, management, and prognosis.^2,3

Management of soft tissue sarcoma aims at curing malignancy by doing limb salvage procedures whenever possible. The cornerstone in the management of STS is surgery aimed at complete tumor resection (defined as R0 resection) since even microscopic tumoral residual in the surgical margins are associated with risk of recurrence and might have an impact on metastatic dissemination and mortality^2,4 Previous studies had proved that the best care for ESTS is combined extensive surgical excision with safety margin and radiotherapy either preoperative (neoadjuvant) or postoperative (adjuvant).^5,6

Most of the previous studies proved that there was no significant difference in the 5-year relapse free survival (RFS) between patients receiving radiotherapy (RT) preoperatively or postoperatively.⁷

Preoperative radiotherapy allows for lower dose of radiation over smaller field which supposed to decrease long-term complications as recurrence or peripheral vascular disease, while postoperative radiotherapy requires higher doses of radiation over larger field to penetrate tissues which may result in some long-term complications such as fibrosis, joint stiffness or edema.⁸

On the other hand, previous retrospective studies had shown that early major wound complications which include wound dehiscence, infection, seroma and burn may be more with preoperative radiotherapy with percentage reaching $40\%$ while decreases with postoperative radiotherapy to reach $15\%$^8,10.

There is no consensus on when to give adjuvant or neoadjuvant radiotherapy in addition to wide surgical resection, and if the early wound complications of preoperative radiotherapy are significant in comparison to postoperative radiotherapy.

We hypothesize that the preoperative radiotherapy is not inferior to postoperative radiotherapy regarding early wound complications as well as recurrence rate, given the fact that it facilitates the surgical resection intraoperatively and may reduce the surgical time.

The aim of this study is to assess and compare in a prospective way between adjuvant and neo-adjuvant regarding surgical preferences and early wound complications which includes dehiscence, infection, seroma and burn. Our aim is to get an approach that facilitates safe surgical resection with the best functional outcomes.

2. Patients and methods

This study was approved by the institutional review board.

The protocol of this study was registered at clinicaltrials.com.

The study was designed as a single-centre, single-blinded parallel-group clinical trial. Patients who presented to our institution between January 2021 and June 2022 were enrolled in the study. Simple randomization was done between patients. The surgeons allocated to both groups were aware of allocated arm, where the patient kept blind till the start of management.

Sample size was calculated by setting the type 1 error alpha at 0.05. a sample size of 10 in each group was calculated to achieve 80 % power to detect margin difference 8%.

• •Inclusioncriteria:

All patients are adult, mature, presented with soft tissue tumour arising from upper and lower extremities, of any size and any histological type by pathological analysis and candidate for limb salvage surgery.

• •
  Exclusioncriteria:

  • o
    Any patient with recurrent ESTS.
  • o
    Received chemotherapy.
  • o
    Received radiotherapy in a nearby region for any cause.
  • o
    Histopathological round cell tumour as it is not sensitive to radiotherapy were excluded from study.
• •Preoperativeevaluation:

Preoperative full clinical evaluation includes complete medical history and history of comorbidities, full clinical examination was done.

Full radiological evaluation was also conducted which includes plain x-ray, MRI with contrast on affected extremities, CT chest with contrast, CT pelvi-abdominal with contrast, PET Scan and biopsy for histopathological analysis was done. Grading of tumour was also determined according to American Joint Committee on Cancer (AJCC)(4). All patients were categorized into two groups: group A (patients who received preoperative radiotherapy) and group B (patients who received postoperative radiotherapy).

• •Preoperative radiotherapy group:

Mapping of tumor size and extension was done using MRI with contrast; preoperative sessions of radiotherapy reaching 50 Gy (GY) in 25–35 sessions according to size of tumour. The surgical procedure was done 6 weeks post radiation as recommended in literature. Full laboratory investigations and anesthesia consultation were done preoperatively. Adequate wide surgical resection was done for limb salvage with adequate soft tissue and skin coverage after excision.

• •Postoperativeradiotherapygroup:
• •The surgical procedure was done after making full laboratory investigations and anesthesia consultation as recommended. Adequate wide surgical resection was done for limb salvage with adequate soft tissue and skin coverage after excision.

Radiotherapy sessions started after complete wound closure and removal of stitches after mapping of margins of area resected with a dose 56-60 GY in 28 fractions over 6 weeks.

• •Post-operativefollowup:

In group A,patients were assessed in first 2 days inside hospital for wound soaking and drainage tube until removal of tube, then re-assessed 2 weeks postoperative regarding any signs of surgical site infection(SSI) (redness, hotness, collection or discharge),then 1 month postoperatively for wound complete closure and exclude signs of infection, then 3 months postoperatively for wound dehiscence, swelling or local recurrence and 6 months postoperatively for delayed complications like local recurrence, pathological fractures, edema or joint stiffness.

In group B, the patients will be assessed 3 weeks post radiation regarding wound signs of infection (redness, hotness or discharge) and dehiscence, then 6 weeks post radiation for wound dehiscence and swelling, then 3 months post radiation for local swelling or recurrence and 6 months post radiation for local recurrence, joint stiffness or pathological fractures.

2.1. Statistical analysis

A p value of less than 0.05 was used to determine statistical significance. Data was collected using Google forms, and the results were exported into an Excel spreadsheet. The collected data were revised, coded, tabulated, and entered a PC using Statistical Package for Social Science (SPSS® 25). The mean, standard deviation, and range for parametric numerical data were used; non-numerical data were reported as frequency and percentage. Furthermore, the Student's t-test was used to assess the statistical significance of the difference between the two means. The Mann–Whitney U test was used for non-parametric data. The Chi-squared test and Fisher's exact test were used to examine the relationship between two qualitative variables. Patient survival was presented on a Kaplan–Meier curve and was estimated using the log-rank test.

3. Results

Twenty-two patients were included in the clinical trial: 12 in Group A and 10 in Group B. The mean age was 46.4 in group A and 45.33 in group B. Duration of follow-up ranged between 6 and 12 months in both groups, with a mean duration of 6.8 months in group A and 7.3 months in group B.

Patients were 16 males & 6 females, all patients were presented with single lesion except for one patient was presented with 2 masses in the anterior and posterior compartments of thigh. Thigh tumors were about 55 % of all tumors (11 patients in both groups). Regarding type of the tumour, 11 patients had liposarcoma (50%), 5 patients had myxoid undifferentiated sarcoma (22.7%), 4 patients had synovial sarcoma (18%), with single case of malignant peripheral nerve sheath tumour and single case of leiomyosarcoma as shown in Table 1.

Table 1.

Characteristics of patients in both study groups.

Variable	Postoperative radiotherapy (N = 12)	Preoperative radiotherapy (N = 10)	p-Value
Age (years), median (IQR)	47.0 (36.0–55.0)	43.5 (37.0–55.0)	0.974a
Sex, n (%)			>0.999b
Female	3 (25.0%)	3 (30.0%)
Male	9 (75.0%)	7 (70.0%)
DM, n (%)	3 (25.0%)	3 (30.0%)	>0.999b
Follow-up time (months)	6.8(6.0–8.0)	7.3 (6.0–9.0)	0.556a

IQR = interquartile range, n = number.

^aMann-Whitney U test.

^bFisher's exact test.

10 patients were staged as type IA, 6 patients were stage IB, 4 patients were stage IIA, single patient as type IB and single patient as type III. The mean SUV max for the tumors in group A was 5.9 ± 2.6 and was 3.42 ± 1.51 in group B as shown in Table 2.

Table 2.

Characteristics of the tumor in both study groups.

Variable	Postoperative radiotherapy (N = 12)	Preoperative radiotherapy (N = 10)	p-Value
Site, n (%)			0.610a
Anteriorthigh	4 (33.3%)	2 (20.0%)
Posteriorthigh	2 (16.7%)	2 (20.0%)
Medialthigh	0 (0.0%)	1 (10.0%)
Knee	2 (16.7%)	0 (0.0%)
Shoulder	1 (8.3%)	1 (10.0%)
Arm	0 (0.0%)	2 (20.0%)
Wrist	1 (8.3%)	0 (0.0%)
Multiplesites	1 (8.3%)	0 (0.0%)
Leg	1 (8.3%)	2 (20.0%)
Size, n (%)			0.922b
<5 cm	1 (8.3%)	0 (0.0%)
5 – 10 cm	3 (25.0%)	3 (30.0%)
>10–15 cm	5 (41.7%)	6 (60.0%)
>15 cm	3 (25.0%)	1 (10.0%)
Type of sarcoma, n (%)			0.194a
Liposarcoma	8 (66.7%)	4 (40.0%)
Myxoidsarcoma	1 (8.3%)	4 (40.0%)
Synovialsarcoma	3 (25.0%)	1 (10.0%)
MPNST	0 (0.0%)	1 (10.0%)
Leiomyosarcoma	0 (0.0%)	0 (0.0%)
Tumor grade, n (%)			0.577b
High	4 (33.3%)	3 (30.0%)
Moderate	3 (25.0%)	1 (10.0%)
Low	5 (41.7%)	6 (60.0%)
Tumor staging, n (%)			0.786b
IA	6 (50.0%)	4 (40.0%)
IB	1 (8.3%)	0 (0.0%)
IIA	1 (8.3%)	3 (30.0%)
IIB	3 (25.0%)	3 (30.0%)
III	1 (8.3%)	0 (0.0%)

^aFisher's exact test.

^bLiner by linear association, n = number.

Regarding grading of tumor, about 60% were low grade in group A, 30 % moderate grade and 10 only were high grade dedifferentiated tumors. While about 43 % were low grade, 35 % were moderate grade and 22% were high grade tumors in group B as shown in figure (1).

Fig. 1.

Grading of tumors.

The mean operation time in group A was 52.5 ± 20.03 min and was 67.5 ± 39.97 min in group B, but it was statistically insignificant.

The mean follow up duration in the study was about 7.1 ± 1.93 months. The overall complications rate was detected and analyzed. The rate of complications between the two groups was 30% overall complications in the preoperative group and 41.6 % in the postoperative group as shown in figure (2).

Fig. 2.

Rate of overall complications and wound complications in both study groups.

Secondary surgical intervention was needed in 4 patients, one patient in group A and three patients in group B. Debridement was needed due to wound complications in one case in the preoperative group, Surgery was done for three cases in group B, one was due to fracture after radiotherapy; the patient underwent ORIF. Two patients had local recurrence, one underwent re excision and the other underwent amputation.

• •Woundhealing:

We found that there is significant statistical difference between the two groups in the duration of wound healing as shown in figure (3).

Fig. 3.

Kaplan-Meier curve for time to healing in both study groups.

The mean time for wound healing in group A was about 5.9 ± 2.6 weeks and about 3.42 ± 1.51 in group B with (p value = 0.011) as shown in figure (4).

• •Earlywoundcomplications:

Fig. 4.

Duration till wound healing between both study groups in weeks.

The early wound complications are defined as any complications involving the surgical wound in the first 4 months after surgery. The early wound complications rate was about 30% in the preoperative radiotherapy group and 25% in the postoperative radiotherapy group. Only single case was in the preoperative radiotherapy group (group A) was presented by SSI 1 month after surgical resection, and surgical debridement was needed, while no wound infections occur in the postoperative radiotherapy group (group B).

4 patients in group A were presented with seroma and fluid collection in the operative bed, all were resolved spontaneously without need of drainage or aspiration, the largest was about 10 × 8 cm2 by ultrasound which was absorbed in 12 weeks. Single patient had developed seroma after surgical resection in group B (p value = 0.078).

Two patients in group A were presented with wound dehiscence (20%), while only one patient in group 2 was presented with wound dehiscence (8.33%) with p value = 0.427. As regards burn surrounding wound, no cases were recorded in group 1 while two cases were recorded in group B as it is clarified in Table 3.

Table 3.

Incidence of individual complications in both study groups.

Variable	Postoperative radiotherapy (N = 12)	Preoperative radiotherapy (N = 10)	p-Valuea
Wound infection, n (%)	0 (0.0%)	1 (10.0%)	0.455
Wound dehiscence, n (%)	1 (8.3%)	2 (20.0%)	0.571
Seroma formation, n (%)	1 (8.3%)	3 (30.0%)	0.293
Skin burns, n (%)	2 (16.7%)	0 (0.0%)	0.481
Local recurrence, n (%)	2 (16.7%)	0 (0.0%)	0.481
Reoperation, n (%)	3 (25.0%)	1 (10.0%)	0.594
Pathological fracture, n (%)	1 (8.3%)	0 (0.0%)	>0.999
Muscle weakness, n (%)	1 (8.3%)	0 (0.0%)	>0.999
Nerve injury, n (%)	1 (8.3%)	0 (0.0%)	>0.999
Metastasis, n (%)	1 (8.3%)	0 (0.0%)	>0.999
Mortality, n (%)	0 (0.0%)	0 (0.0%)	NA

^aFisher's exact test.

No statistically significant difference regarding early wound complications rate was found between two groups (p value = 0.652).

• •Otherlocalcomplications:

As regards other local complications, a single case of fracture that occurred in group B in distal shaft femur after wide resection of liposarcoma in anterior and posterior compartment was detected for which ORIF was needed and the fracture was fully united after 4 months. A single case of muscle weakness occurred in group 2 after resection of liposarcoma in the abductor muscle and the patient had Trendelenburg gait due to abductor muscles resection in the safety margin. A single case of nerve injury occurred (Femoral n. injury) in group B after resection of soft tissue sarcoma in the anterior compartment involving the femoral nerve. There is a statistically significant difference between the two groups (p value = 0.024 as shown in figure (5).

• •Localcontrolandsurvivalrate:

Fig. 5.

Incidence of individual complications in both study groups.

We found no significant difference between the two groups regarding recurrence rate (p value = 0.176) and the survival rate, there were only 2 cases in group B presented with recurrence for which one underwent re-excision, and the other underwent amputation.

4. Discussion

ESTS (extremity soft tissue sarcomas) are rare malignant tumors that represent less than 1% of whole malignant tumors, but it is always considered challenging cases that require multidisciplinary approach for management, taking in considerations the type of tumour, grading, histological grading, metastasis and site of tumor.^5,9

There is no consensus as regard management of ESTS for when radiotherapy is given due to the risk and complications of radiotherapy and its effect on the surgical wound, as well as the skin and vasculature of surrounding area.¹²

Preoperative radiotherapy is beneficial as it downsizes the tumor, creates pseudo capsule and facilitates resection. It also allows giving the patients lower doses of radiation to minimize long-term complications of radiotherapy.^13,14

The previous studies had focused mainly on the overall survival rate and rate of recurrence between preoperative and postoperative radiotherapy and showed no significant difference between both groups as discussed before in several studies.^7,11,15,16

O'Sullivan et al.,¹¹ showed that preoperative radiotherapy is associated with a higher risk of wound complications than postoperative radiotherapy, that about 14 of 88 preoperative patients (35%) compared with five of 94 (17%) postoperative patients had developed major wound complications that needs secondary intervention.¹¹

In a study done on 50 patients, Ruber et al.,¹³ detected early wound complications in patients with soft tissue sarcoma that received preoperative radiotherapy with intensity modulated technique, the rate of complications was 20%.

• •Majorwoundcomplications(MWC):

The term major wound complications refer to a wound complication requiring any of the following.

• oComplications requiring a surgical intervention for wound repair (debridement, abscess drainage and secondary wound closure through plastic surgical flap reconstruction or split skin graft (SSG))
• oNon-surgical wound management including invasive procedure (seroma aspiration), readmission for the intravenous administration of antibiotics.
• oPersistent deep wound packing (>120 days) or requiring hyperbaric oxygen therapy to obtain wound closure.¹³

Collier et al.,⁶ did a single institutional retrospective study over 10 years, for the patients with ESTS receiving preoperative radiotherapy, surgery was done after 6 weeks interval to detect the rate of major wound complications (MWC) and analyze if longer interval may decrease the risk of MWCs. Fifty-four patients were included with a median follow-up of 32 months, MWCs were observed in 15% of patients and 88% occurred within 40 days. Predictors for MWCs on multivariate analysis were peripheral vascular disease (P = 0.03), location in the medial compartment of the thigh (P = 0.03), and neurovascular involvement (P = 0.03).⁶

The most important confounding factor that may affect the results regarding wound complications is the fractions of radiotherapy as in the study by O'Sullivan B. et al.¹¹ the dose was fractionated in only 2 sessions and postoperative boost was also added. Also, study was done by Ruber et al.,¹³ was done on both truncal and extremity soft tissue sarcoma and does not make a comparison between preoperative and postoperative radiotherapy regarding wound and local complications.

Collier et al.,⁶ performed a retrospective study on patients who received preoperative radiotherapy in STS to prove that increasing duration before surgery may improve the functional outcome and decrease the rate of wound complications. However, this study did not discuss the size and site of the tumors, didn't compare between pre and post operative radiotherapy and it is a retrospective study. In a retrospective study by Stevenson et al.,⁷ done on 127 patients, 58 patients (45.7%) in Group I (preoperative radiotherapy) and 69 patients (54.3%) in Group II (postoperative radiotherapy). Twenty-three patients (39.7%) in Group I and 14 patients (20.3%) in Group II developed a MWC (p value = 0.02).

Preoperative radiotherapy was identified as an independent predictor for MWC development.¹⁶ This study corroborates the increased MWC risk following preoperative radiotherapy in ESTS. Studer et al.,¹⁶ found a wound complication rate of 7% in the presented cohort, and a local control rate of 100% in treatment-naive patients with preoperative IMRT for STS. The low wound complications rate found in this study was lower than the postoperative and mainly the preoperative non- (intensity modulated radiotherapy) IMRT arm of the Canadian prospective randomized clinical trial (7% vs. 17% and 35%, respectively).⁷

Comparing these results to what we had done, we did a prospective comparative randomized clinical trial between the two groups, group A (preoperative radiotherapy) and Group B (postoperative radiotherapy). The preoperative group followed the intensity modulated technique (25–30 sessions) with 5–6 weeks duration interval before surgery to minimize the risk of wound complications. The early wound complications rate was about 30% in the preoperative radiotherapy group and 25% in the postoperative radiotherapy group. The preoperative group was about 30% (3 cases) two of them were presented with wound dehiscence that doesn't need secondary intervention and spontaneously wound closure had occurred with continuous dressing and close follow-up. The other case was infected and surgical wound debridement was needed, aggressive debridement was done, and IV antibiotics were given according to culture and sensitivity, also histopathological specimen was analyzed to exclude early recurrence or tumor remnant. The rate of complications of post operative group was 25 %. One single case was presented with wound dehiscence that resolved spontaneously within 8 weeks. The other two cases were presented postradiotherapy sessions with burn around the wound for which continuous dressings were done till complete resolution and healing. The wound complications rate between both groups were statistically nonsignificant with p value 0.652.

• •Confoundingfactors:

As regards the other confounding factors, Lazarev et al.,⁹ had done analytical retrospective cohort study on 9604 patients: 7246 (75.4%) received postoperative and 2358 (24.6%)-preoperative RT and found that use of preoperative RT increased over time, from 16.8% in 2004 to 29.7% in 2012. Multivariate analysis revealed that preoperative RT utilization increased with tumor originating in lower extremities, and size of tumor >10 cm tumors. Statistical analysis revealed no difference between the two treatment cohorts.⁹ However, chemotherapy was added in most of cases, and it was not only on extremities and that may affect the results and change the rate of complications. There was also a tendency to use preoperative radiotherapy with large lesions which may affect the outcomes while post operative radiotherapy was used with small lesions.

A retrospective study by Tseng et al.,¹⁸ 173 patients underwent preoperative RT. One or more MWCs occurred in 55 patients (32%). Wound complications were more likely in patients with lower extremity (49/138, 36%) than upper extremity (6/35, 17%) with P value = (0.03). Another retrospective study was done by Levy et al., 17 on 64 patients divided into two groups and found 13 patients (20%) had major wound complications independent of location/side of the limbs.¹⁷ But also, chemotherapy and postoperative radiotherapy boost were not excluded and needed in 50%,13%, respectively.

While the most important factor that may affect wound complications following surgical resection of soft tissue sarcomas in extremities is the time of radiotherapy, but the rate of wound complications is decreased after the new techniques of preoperative radiotherapy and time interval between sessions and the surgery, but still there are other confounding factors that may affect wound healing and cause wound complications and may affect the results,¹⁹ size of the tumor is one of the important factor, as It leaves large dead space that may cause seroma and wound collection regardless type of radiotherapy. In our study, 7 cases the tumor size was less than 10 cm, six of them were passed uneventfully, while a single case had infected wound and surgical debridement was done (14.3 %), while in 15 cases the tumor size more than 10 cm, ten cases were passed uneventfully while five case had wound complications (33.3%) as shown in figure (6).

Fig. 6.

Size of tumor in both study groups.

Other confounding factor was the site of the tumor, either it is in the thigh compartments or in any other site in both extremities, tumor was located in thigh compartments in 12 cases, from which 5 cases developed local wound complications (40%), while other 10 cases only single case developed local wound complications (10%).

DM is one of the most important confounding factors that may affect wound healing, but it was recorded in our study with no significant importance on the rate of wound complications p value 0.793.

Other local complications had been detected during radiotherapy either preoperative or postoperative. Mahmoudi et al.,¹⁰ in a study done on 80 patients divided into preoperative and postoperative radiotherapy with the rate of wound dehiscence and infection was not significantly different between the two groups (P = 0.32 for both). Of the late complications, the rate of limb edema and subcutaneous fibrosis was similar in the two groups (P = 0.16 and P = 0.35, respectively). In contrast, the rate of joint stiffness was significantly more in the postoperative radiotherapy group (P < 0.001).¹⁰ In our study, other local complications occurred in three cases with post operative group, case presented postradiotherapy sessions with pathological fracture distal shaft femur with no history of trauma for which open reduction and fixation with retrograde nail was done and it the complete union occur after 3 months uneventfully with no wound dehiscence or infection. Another case was presented by abductor lurch and Trendelenburg gait due to abductor muscle weakness following wide surgical resection. The last case was presented with femoral nerve injury which was involved in the tumor mass and sacrificed during wide surgical resection for which knee extension brace was needed during walking.

The time for wound healing was statistically significant to be higher in the preoperative group 5.9 ± 2.6 weeks than postoperative group 3.42 ± 1.51 weeks with p value 0.011 as shown in figure (7).

• •Survivalrateandlocalrecurrence:

Fig. 7.

Kaplan Meier curve for duration of complications occurrence.

The literature had shown no significant difference between the two groups.²⁰ In our study there were 2 cases only that showed recurrence and needed a second surgery for re excision. However, this point is beyond the scope of the study.

We aimed in our study to do a prospective clinical comparative trial between preoperative and postoperative radiotherapy in patients with extremity soft tissue sarcoma to detect primarily the wound complications, taking in consideration the new technique of low fractionated doses of preoperative radiotherapy with prolonged interval before surgery. This approach may decrease the rate of complications in comparison to the previous studies which was proved to be statistically higher in the pre-operative group. Our results showed no significant difference between the two groups.

The study also assessed the impact of the other confounding factors that may affect wound complications as discussed before. It is difficult to eliminate the confounding factors that may affect the results as the soft tissue sarcoma of extremities is very rare mesenchymal tumor that represent less than 1 % of malignant tumors, and the confounding factors are unmodifiable, however all cases were done in the same institution with the same orthopedic surgical team, and the same oncological team to decrease the confounding factors and bias of the study.

5. Conclusion

No increase in the wound complications rate with preoperative radiotherapy by using low fractionated doses of radiotherapy and increasing interval before surgery to six weeks, although there is increased risk of delayed wound healing time after surgery. The size and site of the tumor may increase the risk of wound complications unrelated to the type of radiotherapy.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflicts of interest/Competing interests

The authors declare they have no conflict of interest in preparing this paper.

Availability of data and material (data transparency)

The authors confirm that all data and materials as well as software application or custom code support their published claims and comply with field standards.

Authors' contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by all authors. The first draft of the manuscript was written by Dr Ziad Khaled Abdallah and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval

This prospective clinical trial study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of Ain Shams University approved this study.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Patients signed informed consent regarding publishing their data and photographs.

The authors state that the manuscript has been read and approved by all the authors and that the requirements for authorship as stated earlier in this document have been met and that each author believes that the manuscript represents honest work.