Demographic, clinical, pathologic and treatment pattern of soft tissue sarcoma at Tikur Anbessa specialized hospital, Ethiopia - retrospective cross-sectional study

Introduction

Soft tissue sarcomas (STS) are a rare group of cancers, accounting for 1% of all solid tumors and 15% of all malignant tumors in children.^1,2 The World Health Organization (WHO) has recognized approximately 70 histological subtypes.¹ The global incidence of soft tissue and extraosseous sarcomas is estimates 96201 in 2021.³ The incidence of STS varies in different countries and regions, with 13,460 new cases and 5350 deaths reported in 2021,⁴ 13,130 new cases in Europe,⁵ 2.91 per 100000 in china. Studies conducted in Nigeria have estimated rates of approximately 0.8 cases per 100,000 individuals for males and 0.5 cases per 100,000 individuals for females.⁶ Nonetheless, the lack of comprehensive cancer registries and diagnostic facilities in these countries hinders accurate assessment of the true prevalence and incidence rates of STS in the region.^6,7

Sub-Saharan Africa, particularly Ethiopia, faces several challenges in terms of healthcare infrastructure and resources for the diagnosis and management of soft tissue sarcoma. She designed and promised several national initiatives to avert the challenges of cancer prevention, diagnosis, and treatment. Since there is no documented evidence in Ethiopia, the prevalence and incidence of soft tissue sarcomas are unknown. As Evidence shows that due to the etiology is unknown and a certain genetic association on average, a general practitioner may only see one sarcoma in their career⁸ and 10% familial neurofibromatosis (linked to mutations in the NF1 gene),⁹ familial retinoblastoma (RB gene mutations),¹⁰ and Li-Fraumeni syndrome (TP53 gene mutations),¹¹ are associated with an increased risk. Additionally, previous radiation therapy can predispose patients to certain sarcomas such as angiosarcomas.

Due to the heterogeneous sites of origin of STS, it is difficult to clearly define the clinical features of the disease (increasing size, a size greater than 5 cm, and pain). As the size increases, the risk of malignancy is more likely to be sarcomas.⁶ The standard approach for the diagnosis of a suspicious mass is percutaneous core needle biopsy. Several cores should be taken to maximize the diagnostic yield. However, incisional biopsy may be necessary on rare occasions, and excision biopsy may be the most practical option for small superficial lesions. To ascertain the grade and stage of the tumor, a histological diagnosis should be undertaken in accordance with the 2013 WHO Classification.³

The diagnosis of pathology is based on immunohistochemistry and morphology. Molecular pathology, such as fluorescent in situ hybridization or reverse transcription polymerase chain reaction, should increasingly be used in conjunction with it to validate diagnoses that are characterized by a particular genetic abnormality, such as an activating mutation, chromosomal translocation, or chromosomal amplification.¹² It might be especially helpful in cases when the histology diagnosis is uncertain or the clinical pathologic presentation is unusual. Nowadays, molecular testing is common to distinguish lipomas from atypical lipomatous tumors or well-differentiated liposarcomas, as well as to confirm diagnoses like Ewing sarcoma, rhabdomyosarcoma, and synovial sarcoma

Customizing treatment based on each patient’s unique histology is becoming more and more feasible. Long-term survival, preventing local recurrence, optimizing function, and reducing morbidity are the main therapeutic objectives. Every patient should have their care overseen by a sarcoma multidisciplinary team (MDT) that has been formally established. The Sarcoma MDT should make decisions regarding surgery, chemotherapy, radiotherapy, and the order of each of these treatments. The sarcoma MDT and the site-specific MDT should have a formal link for site-specific STS (such as gynecoithlogical, head, and neck).¹³

There is great variability in histological subtypes, anatomic sites, and clinical presentation, which makes it a heterogeneous entity and makes it difficult to have a specific histologic diagnosis. Owing to the lack of adequate diagnostics and therapy infrastructure in Ethiopia, early identification of soft tissue sarcoma is challenging. Consequently, most patients in Ethiopia present with advanced-stage disease. Therefore, this study aimed to assess the demographic, clinical, pathological, and treatment patterns of soft tissue sarcoma in Ethiopia.

Methods

Results and Discussions

Results

Socio-demographic related variables of the study participants

A total of 190 patients were included in this study. The median age of the participants was 32 years, and the age group 20-40years was the common age group accounting for 51.1%, of the participants. Similarly, 61.6% were Males, and 56.3% participants were married. About 57.4% of the participants were Orthodox by religion and 39.5% self-employed by occupation. Moreover, approximately 34.7% and 30% of the participants were coming from Oromia and Addis Ababa, respectively ( Table 1).

Table 1. Socio-demographic related variables of the study participants.

variables	Classification	frequency	Percentage
Age	1-20years	31	16.5
	20-40years	96	51.1
	40-60years	51	27.1
	60+years	12	5.3
Sex	Male	117	61.6
	Female	73	38.4
Marital status	Single	60	31.6
	Married	107	56.3
	Divorced	5	2.6
	Widow	2	1.1
	Unreported	16	8.5
Religion	Orthodox	109	57.4
	Muslim	42	22.1
	Protestant	37	19.5
Occupation	Employed	21	11
	self-employed	75	39.5
	Unemployed	31	16.3
	Not reported	63	33.2
Region	Oromia	66	34.7
	Addis Ababa	57	30
	Amhara	35	18.4
	SNNP	25	13.2
	Somalia	3	1.6
	Harari	3	1.6
	Tigray	1	0.01

Clinical presentation site, stage pattern, Histology subtypes and Surgical Margin status related characteristics of the study participants

Approximately 48.9%, 24.7%, and 15.8% of the participant’s clinical presentation sites were primary the extremities, trunk, and head and neck, respectively. Likewise, for histological diagnosis at oncology department, 96.8% came with biopsy results and 3.2% came with FNA results alone, and none of patients had IHC at time of initial presentation. The common histological type was undifferentiated sarcoma, accounting 50% followed rhabdomyosarcoma accounting 15.8% and the third most common histology was synovial sarcoma, accounting 6.3% of the cases. The common stage at presentation in this study was stage IV, accounting 36.3% of the cases, followed by stage III, and accounting 23.7% of the cases. In postoperative pathologic review, of 190 of patients, 30 %, 4.7%, 17.9%, and 46.8% were had negative, positive, unknown, and inapplicable for assessing marigin status, respectively ( Figure I). Mass and pain were the common presenting symptoms (77.9%), followed by painless masses 21.6%). Out Of 190 patients, 38(20%) presented with cough from lung metastasis ( Figure II).

Figure I. Clinical presentation site, stage pattern, Histology subtypes and Surgical Margin status of study participants in percentage.

Figure II. Clinical presentation symptoms by percentage from primary disease in soft tissue sarcoma diagnosed in August 2017-August 2021.

Most of patients 53% of patients had underwent upfront surgery. Of these, 4.7% had received adjuvant chemotherapy. Only 3.2% received adjuvant radiotherapy, and for 17.9% of patients surgery alone was sufficed. Indeed, approximately 35.3% of patients were administered palliative chemotherapy and 1l.6% of patients were administered both palliative chemotherapy and palliative radiotherapy. When it comes to adjuvant treatment of the 101 patients who underwent surgery 15(14.9%) took adjuvant treatment. 6(5.9%) patients took adjuvant chemotherapy and radiotherapy. While 89(46.9%) took palliative chemotherapy from these patients 22(11.6%) received both palliative chemotherapy and palliative chemotherapy. Approximately 15.2% took radiation treatment for different indications. (75.9%) received palliative radiotherapy, and only 6(21%) received adjuvant radiation. Moreover, the results indicated that no patients underwent palliative surgery, surgery after neoadjuvant therapy, definitive radiotherapy, neoadjuvant radiotherapy, or neoadjuvant chemotherapy. With regard to dose, 6patients as adjuvant treatment, 4/6 received 60 GY radiotherapy, and 2/6 received 50 GY radiotherapy, while 22 palliative radiotherapy patients, 15/22 (68.2%) they took 20 GY in five fraction, 3/22 patients (13.6%), they took 30 GY in 10 fractions, and 4/22/patient dose was not known. Likewise, patients from chemotherapy 52/89 (52%) received AD regimen (adriamycine+dacarbazine), 20/89(22.5%) received AIM regimen (doxorubicin,ifosphamide, and mesna), the other 7 patients (7.8%) took doxorubicin alone, and 10 patients (11.2%) were not known ( Table 2).

Table 2. Treatment patters among 190 soft tissue sarcoma diagnosed in August 2017-2021 at TASH, Ethiopia.

Treatment pattern	Underwent upfront n(%)	Underwent palliative n(%)	Neoadjuvant n(%)	Adjuvant n(%)	Both adjuvant chemotherapy and radiotherapy after surgery n(%)	Palliative chemo and palliative radio therapy	Dose
Surgery	101(53%)*	No	No		6(3.1%)
Radiotherapy	29(15.2%)	22/29(75.9%)		6/29(20.69%)			- 15/22(68.18%) took 20GY in 5 fraction,3/22(13.64%) took 30 GY in 10 fraction, and 4/22(18.18%) patients dose is not known - 4/6(66.67%) took 60 GYradiotrapy and 2/6(33.33%) took 50 GY
Chemotherapy		89(46.9%)	No	15(7.89%)	6(3.1%)	22/89(24.7%)	- 52/89(58%) took AD AD regimen (adriamycine+dacarbazine), 20/89(22.5%) took AIM regimen (doxorubicin,ifosphamide and mesna),7/89(7.89%) took doxorubicin alone,10/89(11.2%) regimen not known - 10/15(66.67%) took AD regimen (doxorubin+dacarbazine, 3/15(20%)patients took AIM regimen (doxorubicin,ifosphamide and mesna), and 2/15(13.33%) regimen not known

* Represents all the surgery 101/190(53%) were radical surgery.

Discussions

The sex ratio in this study was 1.6:1, the most common age of presentation in this study was 20-40 years of age and the median age was 32 years between men and women, which is almost similar to the study conducted by.¹⁴ The male-to-female ratio in benign tumors was 1.2:1, and among malignant tumors, the ratio was 2:1, which is also similar to that reported previously.¹⁵ The most common age at presentation in this study was 20-40 years of age and the median age was 32 years. This result is similar to that of a previous study conducted at Jimma University.¹⁶ In contrast, the results of this study differ from those of a study conducted in Korea, in which the most common age group was 50–60 years.¹⁷ This difference may be due to the longer life expectancy in developed countries.

Mass and pain were the common presenting symptoms (77.9%), followed by painless masses 21.6%). Out Of 190 patients, 38(20%) presented with cough from lung metastasis. This study also had a similar outcome to that of a retrospective study on the clinical presentation of soft tissue sarcoma.¹⁸ Similarly, the extremity was the common site (48.9%), followed by trunk (24.7%) and head and neck (15.8%), which is almost similar to the reviews done by.^15,19

With regard to the types of histology, the common histological type was undifferentiated pleomorphic sarcoma (50%), followed by rhabdomyosarcoma (15.8%), and the third most common histological subtype was synovial sarcoma (6.3%) in this study. The results of this study show that our histology reporting system is not adequate to specify the type of histology and is not sufficient for comparison with other studies.

The common stage at presentation in this study was stage IV accounting (36.3%) of the cases followed by stage III accounting (23.7%) of the cases. Even if the type of histology was predominantly rhabdomyosarcoma, the current study consistent with.²⁰ In contrast to our study, a retrospective review of an orthopedic oncology database identified 1170 patients with newly diagnosed STS, the incidence of metastases at diagnosis was 10% (116 patients); 8.3% (96 patients) had lung metastases on chest CT, and 1.7% (20 patients) had metastases elsewhere.⁶ This difference may be due to the late presentation of our setup in Ethiopia.

this study, 35.3%, 11.6% of the total cases were treated with palliative chemotherapy and both palliative chemotherapy and radiotherapy, respectively about 48.5% of patients had undergone surgery. Of these, 27.7% of patients had undergone surgery and booked for radiotherapy and 17.9% had undergone surgery alone. The remaining 3.2% of the cases were administered adjuvant radiotherapy. The study has also has less surgical treatment pattern compared with other studies, in which approximately 69% of the cases were treated with surgery. And also In this study, only 3.2% of the patients were administered adjuvant radiation, in contrast to study in which 39.5% of the patients were administered adjuvant radiation after surgery.^14,21 This difference may be due to the inadequate availability of radiotherapy in our country and late presentation of our cases.

The Marigin status was performed for patients undergoing surgery in which it was negative in 57% of patients, it was positive 9% of the cases, and 34% of the cases the marigin status of unknown and it contradict with.^6,15,21 The difference may be that many of our patients’ marigin statuses were not reported. This may be due to the lack of multidisciplinary discussion.

Conclusions

The pattern of soft tissue sarcomas in this cross-sectional study showed a heterogeneous distribution in terms of demography, clinical presentation, treatment, and pathological subtypes. Early detection of these potentially fatal soft tissue sarcoma cases allows oncology practitioners to make better clinical decisions for the best clients. Therefore, this study helps to avert the challenges of this rare cancer by reporting the type of histology and advancing strategies for earlier detection of soft tissue sarcoma.

Declarations

Consent for publication

Not applicable.

Authors’ contributions

HD & MA: conceptualization, Data Curation; Formal Analysis; Methodology; Writing – Original Draft Preparation; HD: Software, Visualization, HD, MA & YD: Writing – Review and Editing and YD: Validation and supervision.