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Abstract

Introduction

Treatment of soft tissue sarcomas can profoundly impact on patients’ clinical and functional outcomes, and quality of life (QoL). In this study, we aimed to investigate the factors affecting oncological and functional outcomes in surgically treated lower extremity soft tissue sarcoma patients.

Methods

This retrospective study analyzed 52 patients with lower extremity soft tissue sarcoma treated between 2016 and 2022. All patients underwent surgical excision and radiotherapy, either in the neoadjuvant (n:32, 28 Gy over 10 days) or adjuvant (20 patients, 45 Gy 5 week) setting. QoL was assessed using the QLQ-C30 score, while functional outcomes were evaluated with the Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) scales. Additionally, factors such as tumor location, histological subtype, surgical margins, tumor volume, and oncologic status were analyzed in relation to functional and QoL outcomes.

Results

Patients who received adjuvant radiotherapy had significantly higher mean MSTS and TESS scores compared to those who received neoadjuvant radiotherapy (P = 0.032, P = 0.010, respectively). Patients who received adjuvant radiotherapy had also significantly higher total QLQ-C30 scores and subscale scores for Physical Functioning, Role Functioning, and Social Functioning compared to those who underwent neoadjuvant treatment (P = 0.033, P = 0.005, P = 0.005, P<0.001, respectively). Five-year overall survival was 72%, and local control was 69%. Mortality rate was higher in patient with pelvic tumors and metastatic disease. In the multivariate analysis, only the presence of metastasis was found to have a significant effect on overall survival (P < 0.05).

Conclusion

Our study highlights that tumor location, particularly pelvic involvement, and the presence of metastases are associated with poorer oncologic outcomes in patients with lower extremity soft tissue sarcomas. Additionally, adjuvant radiotherapy, delivered using a conventional fractionation scheme, is linked to better functional outcomes and improved QoL compared to neoadjuvant radiotherapy, which is administered in a hypo-fractionated regimen.

Keywords

quality of life lower extremity soft tissue sarcoma radiotherapy

Introduction

In the past 3 decades, limb salvage has emerged as the preferred approach for treating extremity sarcomas, leading to a significant decline in amputation rates. This shift has been facilitated by advances in diagnostic technologies, along with improvements in pre and postoperative radiotherapy and reconstructive surgical techniques. Consequently, functional outcomes for patients undergoing limb salvage procedures have shown noticeable improvement over time. Assessing functional outcomes in this context poses challenges due to the variability in methodologies across previously published studies. A recent meta-analysis reviewing 37 studies on functional outcome measurement in patients with lower extremity soft tissue sarcomas identified the Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) scores as the most frequently used assessment tools. These scoring systems have become standard metrics for evaluating functional outcomes in this patient population, reflecting their reliability and widespread acceptance in clinical research.¹

The assessment of functional scores and QoL in sarcoma patients serves as a critical component in understanding the impact of the disease and its treatments on individuals’ well-being. Given that lower extremity soft tissue sarcomas (STS) often require complex surgical and oncologic interventions, it is essential to consider not only clinical outcomes but also the impact on patients’ functional status and quality of life—both of which are critical endpoints in the management of these tumors. While the primary goal of sarcoma treatment remains the eradication of malignant cells and prevention of disease progression, attention to functional status is paramount. Surgical reconstruction techniques must be meticulously selected to minimize postoperative complications and promote optimal functional recovery. However, despite advancements in surgical approaches and rehabilitation strategies, achieving ideal functional outcomes can be hindered by factors such as the extent of tissue resection and the inherent limitations of reconstruction methods.^2,3

Radiation therapy (RT), an integral component of sarcoma treatment, offers unique challenges and considerations. Preoperative radiation is often favored in cases where tumors are large and located adjacent to critical neurovascular structures, as it may shrink the tumor and facilitate safer, more effective surgical resection. Tumor type also plays a role; for example, myxoid liposarcomas are highly radiosensitive and respond particularly well to preoperative treatment. Additionally, when there is a high likelihood of close or positive surgical margins, preoperative radiation can help sterilize microscopic disease at the tumor periphery. Another advantage is that preoperative radiation typically requires a lower total dose (ranging from 28-50 Gy) compared to postoperative regimens (which often range from 60-66 Gy), potentially reducing long-term side effects.

Conversely, postoperative radiation is preferred in certain clinical scenarios. In cases of fungating tumors or infected lesions, delaying surgery to administer preoperative radiation may not be ideal. Similarly, in anatomical regions where wound healing is compromised—such as the lower extremities—postoperative radiation avoids the increased risk of wound complications associated with preoperative protocols. If the need for radiation is uncertain before surgery, and clear margins are anticipated, it may be appropriate to defer radiation until final pathology results confirm its necessity. Furthermore, in surgical settings where the tumor was punctured or inadvertently split during resection—even if wide margins were achieved—postoperative radiation may be employed to reduce the risk of local recurrence.

The timing and dosage of radiation—whether administered preoperatively or postoperatively—impact wound healing, tissue viability, and functional recovery. A key study by O'Sullivan et al.⁴ demonstrated that preoperative RT is associated with higher rates of wound complications but may reduce late radiation-associated toxicity. Previous studies have explored alternative methods of delivering preoperative radiation therapy and evaluated adjusted postoperative doses with the aim of minimizing morbidity while maintaining local control rates.^5,6

Additionally, tumor location and size are critical determinants of functional outcomes and oncological prognosis. Tumors located near neurovascular structures or within complex anatomical regions pose significant challenges in achieving clear margins while preserving limb function.⁷

Functional scores such as MSTS and TESS scores provide a standardized assessment of physical capabilities after surgical interventions, while QoL measures help evaluate the broader psychosocial and physical impact of the disease. These scores offer valuable insights into the effectiveness of therapeutic approaches, rehabilitation strategies, and the overall trajectory of recovery for individuals diagnosed with STS. QoL assessments, on the other hand, offer a comprehensive evaluation of various domains including physical, emotional, social, and functional well-being. For sarcoma patients, quality of life measures help elucidate the broader impact of the disease and its treatments beyond clinical outcomes, shedding light on factors such as pain, fatigue, mobility limitations, and psychosocial adjustments.

In this study, we aimed to investigate the factors influencing clinical, oncologic, and functional outcomes in patients with lower extremity soft tissue sarcomas (STS) treated by surgical excision and radiation therapy. While previous studies have predominantly focused on oncologic results, aspects related to patients’ functional recovery and quality of life are often overlooked. Given the impact of functional outcomes and quality of life on long-term patient well-being, our study provides an analysis that evaluates both oncologic outcomes and post-treatment functional performance, addressing a critical gap in the current literature and contributing to a more holistic understanding of patient care.

Material and Methods

Study Design

This retrospective study analyzed 52 patients who underwent surgery and radiation therapy for lower extremity soft tissue sarcomas (STS) at our institution between 2016 and 2022. Institutional Review Board (IRB) approval (Istanbul University, Approval number: E-67690154-050.99-2417 784, Date: 13.02.2024) was obtained. General institutional informed consent, which includes permission for the use of anonymizeds data for research purposes, was obtained from all patients at initial admission. Following IRB approval in February 2024, study questionnaires were administered during routine follow-up visits. The time from surgery to questionnaire completion varied depending on the follow-up duration, ranging from 12 months to 128 months. Only patients who completed the questionnaire were included in the cohort. The study adhered to the STROBE criteria for retrospective cohort studies.⁸

The inclusion criteria consisted of; patients aged ≥18 years who underwent surgical intervention for lower extremity soft tissue sarcomas (STS), having radiation treatment (neoadjuvant or adjuvant), provided informed consent, and had a minimum postoperative follow-up period of at least 1 year.

Exclusion criteria encompassed patients lost to follow-up, those with incomplete medical records, and those diagnosed with concomitant cancers other than sarcoma.

According to our patient recruitment chart, 94 patients did not meet the inclusion criteria. Specifically, 7 patients were under 18 years old, 53 patients did not provide informed consent for the study, 24 patients did not receive radiation treatment, and 10 patients had not reached the 1-year follow-up period. Regarding the exclusion criteria, 38 patients were excluded: 21 were lost to follow-up, 13 had incomplete medical records, and 4 were diagnosed with concomitant cancers other than sarcoma (Figure 1).

Figure 1.

Flow of Patient Recruitment

Outcome Measures

The Musculoskeletal Tumor Society (MSTS) score is a scoring system designed to objectively evaluate the outcomes of surgical interventions for musculoskeletal tumors.⁹ It is a surgeon/clinician determined score, and not a patient reported outcome (PRO) measure. Each category is evaluated with specific sub-scores and the total score ranges from 0 to 30. A score of 23 or greater is considered an excellent result; a score of 15 to 22 points, is a good result; a score of 8 to 14 points, a fair result; and a score less than 8, a poor result.¹⁰ High MSTS scores represent better functional outcomes after surgical intervention, whereas low scores may represent potential limitations and possible decreases in quality of life. Therefore, the MSTS score is used as a reliable tool to evaluate the success of surgical treatment of musculoskeletal tumors and to optimize treatment strategies.¹¹

Toronto Extremity Salvage Score (TESS) is a measurement developed to systematically evaluate the postoperative functional status of lower extremity sarcoma patients who underwent wide resection.¹² This scoring system aims to objectively measure the patient’s activities of daily living, level of independence, and quality of life after surgical intervention.^13,14 TESS are scored between 0 and 100. Gazendam et al¹⁵ categorized TESS values as poor (0-39), fair (40-59), good (60-79) or excellent (80-100). High TESS scores indicate improved functional independence and QoL after surgery, whereas low scores may indicate potential limitations and possible decline in QoL. In this context, the TESS stands out as a reliable and comprehensive tool for evaluating the treatment outcomes of lower extremity sarcoma patients who underwent wide resection.¹⁴

The EORTC QLQ-C30 is a validated measurement tool developed by the European Organization for Research and Treatment of Cancer (EORTC). It is a self-administered questionnaire designed to assess the quality of life (QoL) in cancer patients and, while it provides quantitative data, it is inherently subjective due to its reliance on patient self-evaluation.¹⁶ This scale is designed to assess a wide range of issues related to general quality of life.¹⁷ There are 30 questions in the questionnaire and these questions cover various aspects to assess the quality of life of individuals undergoing cancer treatment objectively and subjectively. These aspects include general health status, physical functioning, mental functioning, emotional functioning, social functioning, and symptom severity. This questionnaire is widely used in clinical research and clinical practice to determine the quality of life of individuals battling cancer and to personalize treatment strategies. According to the general health score, patients were evaluated as poor between 0-49 and good between 50-100.

All functional outcome scores (e.g., MSTS and TESS) were analyzed as continuous numerical variables. No categorical classification or threshold-based grouping was applied in the statistical comparisons.

Clinical or Tumor Data Classification

Patients were categorized according to tumor location, type, type of resection, presence of recurrence, surgical margin, tumor volume, presence of metastasis, primary or flap closure, presence of radiotherapy (RT)(pre/post operative) and chemotherapy (CT). Tumors were categorized into eight groups based on location and anatomical compartments: posterior thigh, anterior thigh, medial thigh, anterolateral leg (anterior and lateral compartments), posterior leg (deep and superficial compartments), foot and ankle, pelvis, and knee. According to the type of tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant mesenchymal tumor, liposarcoma and MPNST were classified in 5 groups. Surgically, they were divided into wide, marginal, and radical resection. Patient tumor volumes were measured using the OsiriX Lite software (https://www.osirix-viewer.com/osirix_plugins/Volume_Calculator/html/index.html), which estimates volume using the spherical formula: (π × diameter³) / 6. A tumor volume threshold of 65 cm³—corresponding to a spherical tumor with a diameter of approximately 5 cm—was used to categorize patients. This cutoff is widely adopted in the literature as a criterion for tumor size classification. All patients underwent both surgery and radiotherapy. Of these, 32 patients (61%) received neoadjuvant radiotherapy, while 20 patients (39%) underwent adjuvant radiotherapy. The radiation dosage and schedule varied slightly between the groups: patients in the neoadjuvant setting received 28 Gy over 10 days, whereas those in the adjuvant setting typically received 45 Gy over 5 weeks.

All patients underwent both surgery and radiation therapy. The decision to administer either preoperative or postoperative radiation was made on an individualized basis by a multidisciplinary tumor board, considering specific patient and tumor characteristics, as outlined in the Introduction section.

Statistical Analysis

All statistical analyses were performed using SPSS Statistics version 28.0 (IBM Corp., Armonk, NY, USA), and a P-value <0.05 was considered statistically significant. The Shapiro–Wilk test was used to assess the normality of data distribution. For comparisons between two groups, the t test was applied to normally distributed variables, while the Mann–Whitney U test was used for non-normally distributed variables. For comparisons involving more than two groups, ANOVA was used for normally distributed data and the Kruskal–Wallis test for non-normally distributed data. The chi-square test was employed for categorical variables. Survival analysis was conducted using the Kaplan–Meier method.

Descriptive statistics are presented as means with standard deviations (SD) for continuous variables, and as counts with percentages for categorical variables. Follow-up duration was calculated from the date of the last sarcoma surgery to the date of questionnaire completion.

All functional outcome scores (e.g., MSTS and TESS) were treated as continuous numerical variables. No categorical transformation or threshold-based stratification was applied during statistical comparisons, ensuring analysis based on the full range of score distributions.

Results

In the study, 52 patients (29 males, 23 females; 42 living, 10 deceased) were included. The mean age of the patients was 55.1 ± 18.8 (ranging from 16 to 89) years. The mean follow-up was 41.4 ± 28.8 months. Among them, 41 patients had primary sarcoma, while 11 had recurrent sarcoma. Two of the recurrent cases were metastatic. (Table 1). MSTS and other PRO were analyzed for only living patients. The mean MSTS score was 22.4 ± 6 and mean TESS score was 81.7 ± 17. The mean QLQ-C30 score was 60 ± 24. Details of scores were shown in Table 2.

Table 1.

Demographic Data

Gender n (%)
Male	29 (55)
Female	23 (45)
Age, years, mean ± SD	55.1 ± 18.8
BMI, mean ± SD	26 ± 5.6
Alive/Death n (%)	42 (80)/10 (20)
Follow-up, months, mean ± SD (min,max)	41.4 ± 28.8 (12.128)
İnitial tumor status, n (%)<
Primary	41 (78)
Recurrence	11 (22)
Tumor location, n (%)
Posterior thigh	15 (23)
Anterior thigh	7 (10)
Medial thigh	14 (22)
Anterolateral leg	4 (6)
Posterior leg	10 (15)
Foot and ankle	8 (12)
Pelvis	2 (5)
Knee	5 (7)
Sarcoma subtype, n (%)
Synovial sarcoma	11 (21)
Undifferentiated pleomorphic sarcoma	13 (25)
Malign mesenchymal tumor	26 (50)
Liposarcoma	1 (2)
MPNST	1 (2)
Resection type, n (%)
Marginal	1 (2)
Wide	47 (90)
Radical	4 (8)
Tumor volume n (%)
125 cm³>	11 (21)
125 cm³<	41 (79)
Closure type, n (%)
Flap closure	16 (30)
Primary closure	36 (70)
Metastasis, n (%)
Yes	16 (30)
No	36 (70)
Surgical margin, n (%)
Positive	1 (2)
Negative	51 (98)
Radiotherapy
Neoadjuvant, n (%)	32 (61)
Adjuvant, n (%)	20 (39)
Adjuvant chemotherapy, n (%)
Yes	36 (70)
No	16 (30)

n: number of patients; SD: Standard deviation; min: Minimum; max: Maximum.

Table 2.

MSTS, TESS and QLQ-C30 in Alive Patients

N = 42 alive patients
MSTS Mean ± SD	22.4 ± 6.8
23 or greater	63.2%
15 to 22 points good result	18.4%
8 to 14 points fair result	13.2%
Less than 8 poor result	5.3%
TESS Mean ± SD	81.7 ± 17.4
Excellent (80-100)	63.2%
Good (60-79)	26.3%
Fair (40-59)	7.9%
Poor (0-39)	2.6%
Global health status Mean ± SD	60.3 ± 23.9
Physical functioning	65.8 ± 27.5
Role functioning	81.1 ± 28.5
Emotional functioning	76.2 ± 29.7
Cognitive functioning	84.2 ± 21.2
Social functioning	85.5 ± 21.3

The patients’ MSTS scores were strongly correlated with TESS levels. Additionally, the Global Health Status and its subscales—Physical Functioning, Role Functioning, and Social Functioning—showed a statistically significant positive correlation with both MSTS and TESS scores (Table 3).

Table 3.

Correlation Among MSTS, TESS and QoL Scores

	MSTS		TESS
	r	P ^a	r	P ^a
TESS	0.686	<0.001	1.000
Global health status	0.522	0.001	0.537	0.001
Physical functioning	0.694	<0.001	0.813	<0.001
Role functioning	0.730	<0.001	0.826	<0.001
Emotional functioning	0.298	0.069	0.312	0.056
Cognitive functioning	0.109	0.514	0.115	0.492
Social functioning	0.620	<0.001	0.548	<0.001

^aSpearman Correlation Analise.

Statistical analyses of demographic data revealed that patients who received adjuvant radiotherapy had significantly higher mean MSTS and TESS scores compared to those who received neoadjuvant radiotherapy (P = 0.032, P = 0.010) (Table 4).

Table 4.

MSTS and TESS in Demographic Data

Variables	MSTS	TESS
Gender
Male	23.4 ± 5.4	82.3 ± 15.0
Female	21.1 ± 8.3	80.9 ± 20.8
P	0.440^a	0.836^a
Surgery margin
Positive	22.3 ± 6.8	81.4 ± 17.6
Negative	26	92
p	-	-
Tumor subtype
Synovial sarcoma	24.0 ± 4.4	89.7 ± 10.1
Undifferentiated pleomorphic sarcoma	21.6 ± 6.6	77.1 ± 17.3
Malign mesenchymal tumor	22.9 ± 7.1	82.0 ± 18.7
Liposarcoma	26	95
MPNST	6	50.3
p	0.550^b	0.286^b
Resection type
Marginal	26	98.8
Wide	22.2 ± 6.9	81.0 ± 17.6
Radical	26	91.0
p	-	-
Tumor location
Posterior thigh	23.8 ± 8.0	84.3 ± 16.5
p	0.077^a	0.314^a
Anterior thigh	23.0 ± 6.0	82.3 ± 15.4
p	0.884^a	0.775^a
Medial thigh	21.4 ± 6.1	82.4 ± 17.5
p	0.419^a	0.891^a
Anterolateral leg	21.0 ± 3.0	78.7 ± 13.9
p	0.292^a	0.416^a
Posterior leg	21.8 ± 6.2	79.8 ± 16.7
p	0.673^a	0.420^a
Foot and ankle	22.8 ± 5.9	87.0 ± 9.8
p	0.951^a	0.764^a
Knee	20.8 ± 12.0	78.5 ± 31.6
p	0.865^a	0.651^a
Tumor Volume(cm³)
125 cm³ >	17.7 ± 9,1	72.3 ± 23.8
125 cm³ <	23.3 ± 6.0	83.5 ± 15.8
p	0.140^a	0.229^a
Metastasis
Positive	21.5 ± 10.4	79.5 ± 19.7
Negative	22.5 ± 6.4	82.0 ± 17.5
p	0.903^a	0.651^a
Closure type
Flap closure	20.4 ± 7.4	79.9 ± 20.0
Primary closure	23.2 ± 6.4	82.5 ± 16.6
p	0.130^a	0.687^a
Adjuvant chemotherapy
Positive	22.7 ± 6.2	83.4 ± 15.1
Negative	21.9 ± 7.8	79.2 ± 20.8
p	0.854^a	0.834^a
Radiotherapy
Neoadjuvant	20.1 ± 7.7	75.1 ± 19.5
Adjuvant	25.5 ± 3.5	90.8 ± 8.1
p	0.032^a	0.010^a

^aMann Whitney U test

^bKruskal Wallis Test #Chi Square Test.

Among the QLQ-C30 subscales, “Social Functioning” scores were higher in patients with a tumor volume greater than 125 cm³ compared to those with a tumor volume below 125 cm³ (P = 0.022). Furthermore, patients who received adjuvant radiotherapy had significantly higher total QLQ-C30 scores and subscale scores for Physical Functioning, Role Functioning, and Social Functioning compared to those who underwent neoadjuvant treatment (P = 0.033, P = 0.005, P = 0.005, P<0.001, respectively) (Table 5).

Table 5.

QLQ-C30 in Demographic Data

Variables	QLQ-C30	Physical functioning	Role functioning	Emotional functioning	Cognitive functioning	Social functioning
Variables	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD
Gender
Male	61.4 ± 22.5	68.5 ± 24.4	84.8 ± 21.1	79.3 ± 30.2	84.8 ± 21.8	85.6 ± 20.8
Female	58.9 ± 26.4	62.1 ± 31.7	76.0 ± 36.5	71.9 ± 29.3	83.3 ± 21.1	85.4 ± 22.7
P^a	0.881	0.789	0.842	0.211	0.818	0.946
Surgery margin
Positive	60.6 ± 24.2	66.1 ± 27.8	80.6 ± 28.7	76.0 ± 30.1	84.7 ± 21.3	85.1 ± 21.4
Negative	50	53.3	100	83.3	66.7	100
Tumor subtype
Synovial sarcoma	63.5 ± 21.3	74.2 ± 24.8	93.8 ± 12.4	77.1 ± 34.1	75.0 ± 30.9	91.7 ± 23.6
Undifferentiated pleomorphic sarcoma	62.1 ± 22.5	63.0 ± 29.6	78.8 ± 28.0	81.3 ± 23.3	89.4 ± 15.4	80.3 ± 27.7
Malign mesenchymal tumor	54.9 ± 26.4	64.3 ± 27.4	80.4 ± 28.4	70.6 ± 33.1	83.3 ± 19.5	85.3 ± 16.5
Liposarcoma	91.7	93.3	100	100	100	100
MPNST	75	26.7	0.0	83.3	100	83.3
p^b	0.547	0.454	0.232	0.706	0.606	0.545
Resection type
Marginal	100	100	100	100	100	100
Wide	59.5 ± 23.6	65.2 ± 27.6	80.1 ± 29.0	75.3 ± 30.2	84.3 ± 21.4	84.7 ± 21.6
Radical	50	53.3	100	83.3	66.7	100
Tumor location
Posterior thigh	70.1 ± 23.2	73.3 ± 30.7	80.6 ± 30.8	77.8 ± 28.1	88.9 ± 14.8	83.3 ± 25.6
p^a	0.084	0.241	0.972	0.884	0.519	0.829
Anterior thigh	58.3 ± 22.6	60.0 ± 23.1	91.7 ± 16.7	89.6 ± 8.0	79.2 ± 16.0	91.7 ± 16.7
p^a	0.792	0.615	0.456	0.641	0.356	0.550
Medial thigh	54.6 ± 27.7	60.7 ± 31.0	81.5 ± 25.6	70.4 ± 36.4	74.1 ± 23.7	83.3 ± 28.9
p^a	0.603	0.580	0.863	0.671	0.083	0.891
Anterolateral leg	58.3 ± 30.0	51.1 ± 26.9	77.8 ± 19.2	67.7 ± 44.7	94.4 ± 9.6	77.8 ± 19.2
p^a	0.891	0.252	0.467	0.889	0.435	0.337
Posterior leg	59.4 ± 22.9	69.2 ± 22.8	79.2 ± 29.2	79.2 ± 35.1	85.4 ± 30.1	83.3 ± 26.7
p^a	0.772	0.914	0.718	0.319	0.393	0.935
Foot and ankle	54.2 ± 20.9	70.0 ± 16.7	88.9 ± 17.2	75.0 ± 26.9	88.9 ± 17.2	94.4 ± 8.6
p^a	0.442	0.762	0.590	0.773	0.594	0.384
Pelvis	-
Knee	52.1 ± 22.9	63.3 ± 45.4	66.7 ± 47.1	66.7 ± 37.9	95.8 ± 8.3	75.0 ± 16.7
p^a	0.401	0.811	0.522	0.589	0.257	0.142
Tumor Volume(cm³)
125 cm³ >	51.4 ± 15.3	45.6 ± 29.0	66.7 ± 36.5	63.0 ± 32.4	75.0 ± 32.9	69.4 ± 22.2
125 cm³ <	62.0 ± 25.0	69.6 ± 26.0	83.9 ± 26.6	78.6 ± 29.0	85.9 ± 18.5	88.5 ± 20.1
p^a	0.275	0.066	0.151	0.127	0.505	0.022
Metastasis
Positive	50.0 ± 20.4	45.0 ± 12.6	66.7 ± 47.1	66.7 ± 33.3	79.2 ± 16.0	87.5 ± 16.0
Negative	61.5 ± 24.3	68.2 ± 27.9	82.8 ± 26.1	77.3 ± 29.6	84.8 ± 21.9	85.3 ± 22.0
p^a	0.374	0.108	0.522	0.220	0.356	0.913
Closure type
Flap closure	59.8 ± 22.3	64.2 ± 30.9	78.8 ± 30.8	73.8 ± 31.5	89.4 ± 26.1	81.8 ± 21.7
Primary closure	60.5 ± 25.0	66.4 ± 26.6	82.1 ± 28.1	77.2 ± 29.5	82.1 ± 19.0	87.0 ± 21.3
p^a	0.795	0.884	0.718	0.921	0.093	0.348
Adjuvant chemotherapy
Positive	57.6 ± 23.0	67.0 ± 24.1	83.3 ± 28.0	75.4 ± 29.8	85.5 ± 20.9	87.0 ± 19.4
Negative	64.4 ± 25.5	64.0 ± 32.9	77.8 ± 30.0	77.4 ± 30.5	82.2 ± 22.2	83.3 ± 24.4
p^a	0.252	0.775	0.393	0.666	0.643	0.772
Radiotherapy
Neoadjuvant	53.4 ± 24.2	55.2 ± 28.4	70.5 ± 32.9	68.7 ± 33.5	82.6 ± 23.3	75.8 ± 23.4
Adjuvant	69.8 ± 20.6	80.4 ± 18.6	95.8 ± 9.6	86.5 ± 20.2	86.5 ± 18.5	99.0 ± 4.2
p^a	0.033	0.005	0.005	0.059	0.658	˂0.001

^aMann Whitney U test

^bKruskal Wallis Test.

To evaluate the factors affecting mortality, 10 patients who died and 42 patients who were followed up were compared with the chi-square test. It was found that, the presence of pelvic tumor and metastasis was significantly higher in the deceased group. We observed only seven cases of local recurrence, accounting for 13% of the total. The 5-year overall survival rate was 72% and local control was 69%. In the multivariate analysis, only the presence of metastasis was found to have a significant effect on overall survival (Figures 2 and 3). Adjuvant and neoadjuvant radiotherapy demonstrated no statistically significant impact on overall survival or local control. Additionally, in the chi square test, variables such as gender, local recurrence, metastasis, and closure type did not show significant differences between the two radiotherapy approaches.

Figure 2.

Kaplan Meier Analysis for Overall Survival and Local Control

Figure 3.

Effect of Metastasis on Survival

Discussion

The most important strength of this study lies in its highly refined patient population. All included patients had lower extremity soft tissue sarcomas and were treated with both surgery and radiation therapy, creating a homogeneous cohort. This strict selection allows for a focused evaluation of the impact of treatment modalities—specifically surgery and radiation—on functional outcomes. Notably, functional scores were lower in patients who received preoperative radiation therapy, whereas those who underwent postoperative radiation showed better functional scores. While this finding does not allow for a definitive conclusion that postoperative RT is superior, it provides an important perspective and raises relevant questions. We aim to explore this further in the following paragraphs.

The functional outcomes and QoL in lower extremity soft tissue sarcoma (STS) patients can be influenced by several factors such as tumor location, volume, resection type, and radiotherapy (RT) or chemotherapy (CT). In this study, only radiation therapy was found to affect the functional status and QoL of the patients. Both preoperative and postoperative radiotherapy provide comparable local control and survival rates. However, their toxicity profiles differ, as preoperative radiotherapy increases the risk of wound complications, whereas postoperative radiotherapy may lead to joint stiffness, fibrosis, and contractures. O’Sullivan et al conducted a prospective randomized study investigating the benefits and drawbacks of preoperative vs postoperative radiotherapy in limb soft-tissue sarcomas. Their findings showed that overall survival was slightly better in patients who received neoadjuvant RT compared to those who had adjuvant treatment. However, neoadjuvant RT was associated with a higher risk of wound complications.⁴ While radiation therapy is primarily aimed at reducing local recurrence rather than improving overall survival, the timing of RT should be carefully individualized based on patient and tumor characteristics. Another study conducted by Davis et al¹⁸ investigated functional outcomes at 1 year postoperatively in patients with soft tissue sarcoma who received either preoperative or postoperative radiation therapy. Their findings demonstrated no significant differences in MSTS, TESS, or SF-36 scores between the two groups.¹⁸ Townley et al found similar results which is no significant difference in the functional scores of patients who received neoadjuvant RT and those who did not.¹⁹ However, bone sarcomas were also included in this study. Our findings revealed that neoadjuvant RT was associated with unfavorable functional outcomes, as giving by lower scores in both MSTS and TESS, along with diminished quality of life outcomes. Götzl et al and Kask et al have demonstrated that patients undergoing neoadjuvant RT exhibit lower functional scores, a finding that aligns with our own results.^20,21 This discrepancy underscores the need for further research with a more homogeneous cohort to better assess the functional impacts of neoadjuvant RT, particularly in soft tissue sarcomas.

Another issue we would like to discuss is the fractionation of radiotherapy (RT). Conventionally, a 5-week neoadjuvant or adjuvant RT regimen has been considered the standard of care for patients. However, in the last decade, hypo-fractionated approaches have gained popularity.⁵ The optimal number of fractions remains a topic of ongoing debate, as studies continue to compare the efficacy, toxicity, and functional outcomes of different fractionation schedules.^6,22 This study provides insight by comparing neoadjuvant hypo-fractionated RT and adjuvant classical RT regimens regarding the functional status of soft tissue sarcoma (STS) patients. Further research is needed to determine the best approach to maximize tumor control while minimizing adverse effects.”

The 5-year overall survival rate in our study was 72%. This is consistent with the findings of Popov et al, who reported a 5-year overall survival of 76% in their investigation of lower extremity sarcomas.²³ Moreover, Potter et al conducted a comprehensive analysis involving 363 patients, with a mean follow-up period of 82 months. They reported a 5-year survival rate of 82.6% and a 10-year survival rate of 71%.²⁴ It’s worth noting that Potter et al's study included 30% of patients with upper extremity sarcomas, thus encompassing a broader spectrum beyond just lower extremity cases. Local recurrence rates reported in the literature range from 10% to 18.6%, with Sheoran et al, Shukla et al, Trovik et al, and Bansal et al presenting findings within this range; our study’s recurrence rate of 13% aligns with these results, demonstrating consistency with existing research.^25-28

Age and gender were not associated with functional outcomes in our study. Advanced age and high BMI were shown to be determinants of functional scores in a study by Kask et al.²¹ Heaver et al reported that advanced age decreased functional scores.²⁹ In the analysis of patients with lower extremity STS only, gender did not affect postoperative functional outcomes and quality of life.^21,30

Patients with large tumor volumes and those who undergo radiotherapy often require flap closure. Kang et al conducted a comparison between flap reconstruction and primary closure, revealing that reconstruction was linked to poorer outcomes.³¹ Surprisingly, in our study, the provision of closure type did not correlate with functional outcomes.

Gerrand et al discovered that the anatomical location of the tumor was not a predictor for MSTS and TESS scores. In their study, nine anatomical regions were defined, including the groin, hip, anterior thigh, medial thigh, posterior thigh, popliteal fossa, posterior leg, anterior leg, and foot and ankle.³² Similarly, our findings indicate that tumor location in the lower extremity did not affect MSTS scores or other patient-reported outcomes (PROs). Two deceased patients with pelvic soft tissue sarcoma were excluded, as only the surviving patient was evaluated functionally. In our study, metastasis was found to be the most effective factor in predicting mortality. Sawamura et al showed that metastasis is a predictive factor for mortality in pediatric STS.³³ Krisnan et al found that metastases in STSs lead to a decrease in functional scores and have a poor prognosis.³⁴

Stefanovski et al examined prognostic factors in a series of 395 patients. Tumor grade, size and advanced age were reported to have a poor prognosis, but the main determinant of local recurrence was positive surgical margin.³⁵ In our study, type of surgical margins did not cause any change in functional and quality of life.

Tumor size is 1 of the important prognostic parameters in lower extremity soft tissue sarcomas. In many studies in the literature, an increase in tumor size or volume has been associated with poor functional outcomes.^23,27,36 However, we found that tumor volume did not affect functional outcomes and quality of life in our study. We attributed this to the fact that high-volume tumors were predominantly found in the group with mortality and that functional scores and quality of life were not evaluated in the group with mortality.

Our study has some limitations, including its retrospective nature, wide age range, heterogeneity of patients and lack of preoperative data. Another limitation is the multiple comparisons made within a modest sample size, which may affect the generalizability of the findings. However, the strengths of our study were that it examined lower extremity sarcomas in isolation, anatomical location, evaluation of tumor type, functional scores and quality of life were evaluated together.

Conclusion

Our study indicates that pelvic tumor involvement and metastases correlate with poorer oncologic outcomes in lower extremity soft tissue sarcomas. Additionally, neoadjuvant radiotherapy, administered in a hypo-fractionated regimen, is associated with lower functional scores and reduced quality of life compared to adjuvant radiotherapy, which follows a conventional fractionation scheme. This comparison provides insight into the impact of different radiotherapy fractionation strategies. Additionally, this study is expected to help fill the gap in the literature regarding information on functional status and quality of life in this patient population.

Supplemental Material

Supplemental Material - Functional and Oncological Outcomes in Patients With Surgically Treated Lower Extremity Soft Tissue Sarcoma

Supplemental Material for Functional and Oncological Outcomes in Patients With Surgically Treated Lower Extremity Soft Tissue Sarcoma by Zeyneb İrem Yuksel Salduz, Yaşar Samet Gökçeoğlu, Ayşe Nur İncesu, Serkan Bayram, Ahmet Salduz in Cancer Control.

Supplemental Material

Supplemental Material - Functional and Oncological Outcomes in Patients With Surgically Treated Lower Extremity Soft Tissue Sarcoma

Supplemental Material

Supplemental Material - Functional and Oncological Outcomes in Patients With Surgically Treated Lower Extremity Soft Tissue Sarcoma

Footnotes

ORCID iDs

Zeyneb İrem Yuksel Salduz

Ahmet Salduz

Ethical Considerations

The study was approved by the Institutional Review Board of İstanbul University, Department of Orthopedics (E-67690154-050.99-2417 784) and conducted in accordance with the Declaration of Helsinki (2013 revision). General institutional informed consent, which includes permission for the use of anonymized data for research purposes, was obtained from all patients at initial admission. Following IRB approval in February 2024, study questionnaires were administered during routine follow-up visits.

Author Contributions

Zeyneb İrem Yuksel Salduz: Conceptualization (Equal) Methodology (Equal) Supervision (Equal) Validation (Equal) Visualization (Equal) Writing – original draft (Equal) Writing – review & editing (Equal). Samet Gökçeoğlu: Data curation (Equal) Formal analysis (Equal) Methodology (Equal) Software (Equal) Validation (Equal) Writing – original draft (Equal) Writing – review & editing (Equal). Ayşenur İncesu: Data curation (Equal) Formal analysis (Equal) Investigation (Equal) Methodology (Equal). Serkan Bayram: Data curation (Equal) Formal analysis (Equal) Investigation (Equal) Methodology (Equal) Writing – original draft (Equal) Writing – review & editing (Equal). Ahmet Salduz: (Corresponding Author) Conceptualization (Equal) Data curation (Equal) Formal analysis (Equal) Investigation (Equal) Methodology (Equal) Project administration (Equal) Resources (Equal) Supervision (Equal) Validation (Equal) Visualization (Equal) Writing – original draft (Equal) Writing – review & editing (Equal).

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets generated for this study are available on re-quest to the corresponding author.*

Supplemental Material

Supplemental material for this article is available online.

Appendix

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Supplementary Material

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