Abstract
Background
Currently there is limited literature available on fungating soft tissue sarcoma and its effect of outcomes. In the current study we evaluated the surgical management and oncologic outcomes of patient with fungating soft tissue sarcoma.
Materials and methods
This was a retrospective observational study of patients with fungating sarcoma between January 2015 till January 2019 at a tertiary cancer care centre. A total of 59 patients were considered of which 16 had metastasis at presentation. The duration of symptoms prior to presentation averaged 10.2 months (median, 7.2months; range, 1–57 months). Median tumor length was 10 cm.
Results
56% patients underwent amputation and 44% were treated with limb salvage. Following limb salvage surgery in10 cases primary closure of defect was performed and 6 cases required skin grafting for closure of defect. In 6 patients local flap was used for coverage of defect and 4 patients required free flap surgery. Two-year overall survival (OS) of the study cohort were 52.2% and 58% respectively. Two-year disease free survival (DFS) and OS in 43 non metastatic patients at presentation was seen in 58%(95% CI,38%–74%) and 66.5%(95% CI,42%–81%) respectively. The two-year disease OS in 16 patients with metastasis at presentation was 33.2 %. On univariate analysis, tumor size and metastatic at presentation had significant effect on survival.
Conclusion
Tumor size and metastatic at presentation has significant impact on survival in these patients. The oncologic outcomes including Disease free survival, overall survival and local recurrence rates similar amongst the two surgical modalities (amputation versus limb salvage). Amputation rates are more amongst fungating soft tissue sarcoma but limb salvage can be attempted whenever feasible keeping tumor free surgical margins under consideration.
Keywords: Fungating sarcoma, Soft tissue sarcoma, Limb salvage, Amputation, Metastasis
1. Introduction
Soft tissue sarcomas are uncommon tumors and account for less than 1% of all newly diagnosed malignancies.1, 2, 3 Sarcomas are believed to arise de novo and the metastasis is thought to be occurring through hematogenous, lymhphogenous route. The metastases at the time of initial presentation are uncommon and the lungs are the most common site of initial metastases.
Sarcoma which protrudes through the skin are called fungating sarcomas. “Fungate” means “to grow rapidly like fungus”.1,6 Apart from Kaposi sarcoma and dermatofibrosarcoma protuberans which primarily arises from skin and subcutaneous tissues, direct skin fungation by soft tissue sarcoma is relatively rare.1 In oncology fungation means malignant tumor ulceration because of a locally aggressive tumor involving and protruding from the skin.1 The prognostic value of ulceration is well studied in carcinomas such as breast cancer and melanoma.
In majority of developing countries of Asian subcontinent there is limited data available on epidemiology, treatment pattern and outcomes.2 Quek et al., in 2015 published results from the soft tissue sarcoma in the Asia Pacific Region (STAR) region.2 They had evaluated the data of 635 patients in 5 Asian countries that included the epidemiology, treatment patterns and outcomes.2 It demonstrated a median overall survival of 11.7 months in patients who presented with metastatic STS, a result comparable with outcomes from the Western literature.2 There is neglect in neglect in treatment due to delayed presentation and the causes of delay includes low socioeconomic status, poor literacy rate and availability of limited health care hospitals. In large fungating tumor with initial metastasis, surgery can be done either in form of limb salvage or amputation. The management of soft tissue sarcoma is multimodality involving surgeon, medical and radiation oncologist. Surgery aims at achieving local disease control and free tumor free surgical margin. Limb-salvage surgery, can be performed, but in very large, neglected, fungating or aggressive tumor limb salvage may not be feasible thus requiring amputation. In large fungating tumors, skin cover can be done by split thickness skin graft, local flap or free flap. In previous studies, more than 50% of patients with fungating sarcoma developed systemic metastasis and ultimately succumbed to disease thus responsible for overall poor survival.2, 3, 4 Local disease control is also poor with local relapses ranging from 33% to 92%.5
Fungation is a bad prognostic indicator due to apparent aggressive nature of the disease process. Malignant tumor ulceration is an independent predictor of a poor prognosis for patients with a high-grade soft-tissue sarcoma.1
Currently there is limited literature available on fungating soft tissue sarcoma and its effect of outcomes. The purpose of the present study was to evaluate the surgical management and early oncologic outcomes of patient with fungating soft tissue sarcoma treated at a tertiary cancer centre.
2. Materials and methods
This is a retrospective study from a prospectively maintained database of operated fungating soft tissue sarcomas between January 2015 till January 2019 at a tertiary cancer center in a tertiary Asian cancer centre. Study was undertaken after approval from institutional review board. Patient's previous history of treatment records, outpatient records, inpatient records, imaging studies, pathology reports were reviewed. The primary study group consisted of 59 patients who presented to our institute with fungating soft tissue sarcoma (Fig.-1). All patients in the study had been under follow up for a period of minimum one year. Scrutinized variables included patient age and sex, tumor size, disease site, metastasis at presentation, pathological fracture histo-pathologic diagnosis. Punch biopsy/Trucut biopsy was done to prove histology. All Patients had undergone local site Magnetic Resonance Imaging (MRI) and Contrast enhanced computed tomography(CECT) of thorax as part of metastatic work up. MRI brain and Bone scan was done if patient presented with symptoms of brain metastasis and skeletal metastasis. Management in all patients was planned after multidisciplinary tumor board discussion.
Fig. 1.
Flowchart of consecutive patients with Soft tissue sarcoma along with Non Fungating cases and Fungating cases.
The surgical procedure either amputation or limb salvage was carried out in all patients. The primary aim of surgery was complete excision of tumor with tumor free surgical margins. Limb salvage was attempted in whom critical neurovascular structures were free and good functional limb was anticipated after surgery with acceptable reconstruction.
Chemotherapy was planned on the basis of tumor histopathology type as per institutional protocol. Adjuvant radiotherapy and chemotherapy was given as advised after pathological review in tumor board. Adjuvant radiotherapy was given in all patients in view of high grade nature of the tumor.
Outcome measures included local recurrence of disease, systemic metastases and death. Disease free Survival[DFS] is duration from date of surgery till appearance of recurrence. Overall survival(OS) is time from date of surgery till last objective evidence of follow up or death.
3. Post-operative surveillance
Local site imaging in the form of Magnetic resonance imaging was used three months after the surgery, every three to four months for two years, and every six months till now. Metastatic Surveillance in the form of chest radiographs every three monthly and computed tomography scans every six monthly were done postoperatively.
Disease free survival (DFS) and overall survival (OS) rates were analyzed using the Kaplan-Meier method with calculation of 95% confidence intervals (CI).
Statistical analysis was done with STATA for Windows, version 16 (Stata Corp., College Station, Texas). Demographic analysis was done with descriptive statistics. Difference between rates and proportions of occurrence were assessed using chi-square test. Survival analysis was done with Kaplan Meier analysis. Univariate analysis was done with log rank test. P value of less than 0.005 was considered significant.
4. Results
Out of 59 patients in the study 38(64.4%) were male and 21(35.5%) were female. The mean age of the study cohort was 61.2years (median, 34 years; range, 17–74 years). The duration of symptoms prior to presentation averaged 10.2 months (median, 7.2months; range, 1–57 months). Upper limbs were affected in 11(18.6%) patients, lower limbs in 43(72.9%), pelvis in 2(3.4%) patients and shoulder in 3(5%) patients. 33(55.9%) patients underwent amputation and in 26(44.1%) patients underwent limb salvage surgery. All patients had tumor free surgical margin on final histopathology. The most common histology was synovial sarcoma (28.8%). Metastasis at presentation was present in 27.1% patients (n = 16). (Table-1). The wide resection of fungating sarcoma with limb salvage surgery was performed in 26 patients of which in 10 cases primary closure of defect was performed. In six patients local flap was used for coverage of defect(Fig. 3, Fig. 4). Six patients required only skin grafting for closure of defect(Fig. 5, Fig. 6, Fig. 7). In four patients free flap was performed to achieve the closure of defect.
Table 1.
Characteristics of the Fungating soft tissue sarcoma patients.
| Characteristics of patients(n = 59) | Patients n(%) |
|---|---|
| Gender | |
| Male | 38(64.4) |
| Female | 21(35.6) |
| Median age at diagnosis, years | |
| <35 | 30(50.84) |
| >35 | 29(49.15) |
| Tumour localization | |
| Lower limb | 43(72.9) |
| Upper limb | 11(18.6) |
| Shoulder | 3(5.08) |
| Pelvis | 2(3.38) |
| Histological subtype | |
| Synovial sarcoma | 17(28.8) |
| Angiosarcoma | 12(20.3) |
| Malignant fibrous histiocytoma | 11(18.6) |
| Synovial sarcoma | 5(8.5) |
| Malignant peripheral nerve sheath tumor | 4(6.8) |
| Leiomyosarcoma | 3(5.1) |
| Liposarcoma | 3(5.1) |
| Myxofibrosarcoma | 1(1.7) |
| Fibro sarcoma | 1(1.7) |
| UPS | 1(1.7) |
| Rhabdomyosarcoma | 1(1.7) |
| Metastasis at presentation | |
| Yes | 16(27.11) |
| No | 43(72.9) |
| Surgical management | |
| Amputation | 33(55.9) |
| Limb salvage | 26(44) |
| Limb salvage surgery(n=26) | |
| Direct closure | 10(38) |
| Skin grafting | 6(25) |
| Local flap | 6(25) |
| Free flap | 4(15) |
Fig. 3.
a: Clinical image showing fungating sarcoma over anterior aspect of proximal tibia; b: Wide resection of tumor; c: defect created following resection of tumor; d: Medial gastrocnemius flap is harvested.
Fig. 4.
a: Medial gastrocnemius flap is used to cover the defect; b: closure of part of defect with direct suturing; c: skin graft placed over medial gastrocnemius flap.
Fig. 5.
a: MRI of a patient with fungating soft tissue sarcoma over scapular region: Clinical image of fungating mass over scapular region; c: Fungating mass covered with cotton gauze and ioban (impervious drape material); d: Skin incision marked around the fungating mass covered by cotton gauze and ioban (impervious drape material).
Fig. 6.
a: Resected specimen anterior surface; b: Resected specimen posterior surface.
Fig. 7.
a: Defect created following resection of tumor; b: Partial closure of defect following suturing; c: Skin graft placed to cover remaining defect.
5. Survival analysis
The survival analysis of the patients was performed and disease free survival and overall survival were calculated (Fig. 2, Fig. 3, Fig. 4, Fig. 5). The 59 patients were analyzed by Kaplan Meier method and disease free survival was evaluated. Two-year disease free survival in 43 non metastatic patients was seen in 58%(95% confidence interval,38%–74%) patients (Fig.-8). Two-year overall survival was 66.5%(95% confidence interval,42%–81%)(Fig.-9a). The two-year disease free survival and overall survival in 16 patients with metastasis at presentation was 12.5 % and 33.2 % respectively.
Fig. 2.
MRI of a patient with fungating soft tissue sarcoma over anterior aspect of proximal tibia.
Fig. 8.
Kaplan–Meier curve of the disease free survival for patients of fungating soft tissue sarcoma with non metastatic at presentation(n = 43).
Fig. 9.
a: Kaplan–Meier curve of the overall survival for patients of fungating soft tissue sarcoma with non metastatic at presentation(n = 43) b: Kaplan–Meier curve of the overall survival for all patients of fungating soft tissue sarcoma (n = 59).
Median tumor length was 10 cm. 20.9 patients were given neoadjuvant chemotherapy. Amputation was done in 46% patients and limb salvage surgery was done in 54% patients. 25.5% patients received adjuvant chemotherapy and 18.6% patients received adjuvant radiotherapy. Sixteen percent developed local recurrence on follow up. Out of these 7 patients, 4 patients had associated lung metastasis. Resurgeries for local recurrence were done in 3 patients with isolated local recurrences. Of these seven patients with local recurrences, 2(10%) had undergone amputation and 5(21.7%) had undergone limb salvage (p = 0.298). Lung metastasis was resolved in one patient with chemotherapy. Thirty percent developed metastasis on follow up. Of these lung metastasis was most common site of metastasis followed by brain metastasis and bone metastasis. Various factors were assessed for their effect on DFS and OS (Table-2). Histology had a significant effect on overall survival (p = 0.044) but not on disease free survival (p = 0.177).
Table 2.
Demographic and clinical variables with statistical analysis.
| Criteria | Variables | Two year DFS | p- value | Two year OS | p- value |
|---|---|---|---|---|---|
| Age(in years) | >35 (n = 34) | 46% | 0.069 | 27.7% | 0.768 |
| <35 (n = 19) | 79% | 70.8% | |||
| Sex | Male (n = 39) | 48% | 0.169 | 71.6% | 0.753 |
| Female (n = 20) | 72% | 73.5% | |||
| Length of tumor(cm) | <10 cm (n = 24) | 86.1% | 0.001‡ | 79.6% | 0.594 |
| >10 cm (n = 35) | 35% | 43.5% | |||
| Surgical procedure | Amputation (n = 33) | 44% | 0.262 | 71.2% | 0.547 |
| Limb salvage (n = 26) | 68% | 69.4% | |||
| Metastatic at presentation | Metastatic(n = 16) | 12.5% | 0.003‡ | 33.2% | 0.008‡ |
| Non metastatic(n = 43) | 58.1% | 66.5% |
‡ Statistically significant (p < 0.05), DFS, Disease free survival; OS, Overall survival; EFS, Event free survival.
Non metastatic patients had better DFS and OS compared to metastatic patients which was statistically significant. Two-year disease free survival and Overall survival for the whole study cohort including the patients who had metastatic at presentation were 52.2% (95% confidence interval,35%–67%) and 58 %((95% confidence interval,38%–75%) respectively(Fig.-9b). Another factor that had significant impact on DFS was tumor length but its impact on overall survival was not significant but favored the finding that larger tumor had poor survival.
6. Discussion
Sarcoma which protrudes through the skin are called fungating sarcomas. Fungation may be due to long standing tumor neglected by the patient or due to aggressive nature of the tumor. Patients give history of taking alternative medicines for long period and present to cancer center when they don't get relief. Other factor contributing to delayed presentation is the nonspecific nature symptoms till ulceration develops. We performed review of literature and compared the outcomes of current study with the published data (Table-3).
Table 3.
Review of literature: Comparison of various variables and survival outcomes.
| Study | Current Study | M Parry et al.6 | B Potter et al.1 |
|---|---|---|---|
| Origin of Paper(Continent) | Asia | Europe | USA |
| Year of publication | 2023 | 2017 | 2009 |
| Total patients | 292 | 2661 | 170 |
| Patients with fungating sarcoma, n | 59(20.2%) | 86(3.2%) | 24(14%) |
| Sex, n (%) | |||
| Males | 38(64.4) | 39(45.3) | 8(33.3) |
| Females | 21(35.5) | 47(54.6) | 16(66.6) |
| Age at presentation(years) | 61.2 | 68.8 | 64.9 |
| Duration of symptoms prior to presentation, months(range) | 10.2(1–57) | 12.25 (0.75–52) | 13.8(2–132) |
| Tumour size, mean (cm) | 10 | 11.4 | 9.9 |
| Operative Treatment, n (%) | 59(100) | 79(92) | 24(100) |
| Amputation | 33(55.9) | 18(20.9) | 8(35) |
| Limb Salvage | 26(44.1) | 61(70.9) | 15(65) |
| No surgery | 0(0) | 7(8.1) | 0(0) |
| Local recurrence, n (%) | 9(15.25) | 16(20) | 3(13) |
| Metastatic disease at presentation, n(%) | 16(27.11) | 17(20) | 8(33) |
|
Survival outcome(DFS) %,(95 Confidence Interval) |
52.2% (35–67)b | 15.5% (4.6–26.4)a | 34.6% (27.1–42)a |
|
Survival Outcome(OS) %,(95 Confidence Interval) |
58% (38–75)b | 18% (8.2–27.2)a | 19.6% (0–39.2)a |
DFS, Disease free survival; OS, Overall survival.
5year Survival outcome.
2-year Survival outcome.
Parry et al., in 2015 published results from the soft tissue sarcoma had evaluated the data of 2661 and demonstrated a 3.2 % prevalence of fungating soft tissue sarcoma.6 In study by Potter et al. the total number of soft tissue sarcoma were 170 patients out of which 14 % patients had fungating soft tissue sarcoma.1 The results of current study showed that 292 patients were operated during study period and demonstrated a 20.2% a prevalence of fungating soft tissue sarcoma. The higher rate of fungating soft tissue sarcoma in current study may be due to multiple causes. The current study population included majority of patients from lower socioeconomic status and neglect due to unawareness about tumors conditions may have contributed to higher rates of fungating soft tissue sarcoma. The gender distribution in published literature showed higher prevalence of fungating soft tissue sarcoma in females (Parry et al.: 54.6% and Potter et al.:66%). In contrast the current study had higher prevalence of soft tissue sarcoma in males (Males:64.4%). Despite a probability of higher gender inequality in developing population in the apathy to get early treatment this didn't reflect in the results of current study.
Fungation of soft tissue sarcoma has been proven to be a poor prognostic factor.1,6 Patients with sarcoma secondary to chronic osteomyelitis is also suggested to be of poor prognosis associated with fungation.7 Present study reviews various factors impacting survival in fungating sarcoma. Tumor length had statistically significant impact on DFS with length more than 10 cm having worse DFS (93% vs 35%, p = 0.001). Larger tumor had poorer overall survival also but that didn't reach statistical significance (86.6% vs 43.5%, p = 0.547). Young age (<35 years), female sex had a trend towards better survival but this did not reach statistical significance. Metastasis at presentation had significant impact in reducing the DFS and OS. In the present study limb salvage was possible in 53.48%(n = 23) patients and 46.51%(n = 20) underwent amputation in the non-metastatic cohort. Limb salvage is decided by assessing the possibility of saving the neurovascular bundle and giving acceptable reconstruction along with preservation of function without compromising surgical margins. In the present study there is no significant difference between the two surgical modalities on survival. Two-year overall survival in our study cohort was 65% excluding the patients with metastatic at presentation and 58% including the metastatic group.
Study by Parry et al.6 reported 5year survival of 15.5%. Median tumor size 12 cm in the fungating group compared to 10 cm in present study. They compared fungating versus non fungating and established that fungating presentation, size, depth and grade were important prognostic factors. In study by Potter et al.1 5-year disease specific survival excluding patients with metastasis was 58% and 19.6% in the complete fungating sarcoma cohort including metastatic diseases. In the above mentioned studies,1,6 fungation, advanced stage, size more than 10 cm were poor prognostic factors as in our study. Amputation rates were more in fungating sarcoma group in both the studies, but when we analyze specifically the surgical management in fungating sarcoma group it was found that 65% in Potter et al.1 and 77% in Parry et al.6 underwent limb salvage. In our study only 53.5% could undergo limb salvage because of feasibility issues. There was no significant difference in local recurrence rates between amputation and limb salvage in any study including the present study.
Grimer8 suggested that size and metastatic at presentation were important independent factors on survival as was found even in the present study. Younger population generally present with smaller size of tumor thus having better survival as seen in our study but that didn't reach statistical significance. Ferrari et al.9 reported children having better outcome than adults.
Fungation in a sarcoma is either due to neglect by the patient or because of aggressive disease biology. When later is the reason, other manifestations of aggressive biology are also evident like high grade and early distant metastasis. Metastatic at presentation is a poor prognostic factor responsible for statistically significant reduced survival as seen in present study.
Efforts have been made to create awareness and impart education at primary care to raise suspicion about soft tissue sarcoma at early stage leading to timely referral to tertiary center for multimodality management.10 But it is equally important to raise awareness amongst patients who do not present early despite the significant morbidity of fungating sarcoma. Neglect needs to be prevented by appropriate education about the potential morbidity.
7. Limitation of the study
Major limitation is short follow up and retrospective nature thus prone to inaccuracies in data collection but since data was collected from a prospectively maintained database we believe the data to be accurate. Disease biology plays a very important role in prognosis. Different histology contributes to the disease biology in a different manner, thus small sample size of individual histology is another limitation.
8. Conclusion
The prevalence of fungating soft tissue sarcoma in Asian population was higher as compared with from the Western literature. Tumor size and metastatic at presentation has significant impact on survival in these patients. The oncologic outcomes including Disease free survival, overall survival and local recurrence rates similar amongst the two surgical modalities (amputation versus limb salvage). Amputation rates are more amongst fungating soft tissue sarcoma but limb salvage can be attempted whenever feasible keeping tumor free surgical margins under consideration.
Funding
Nil.
Ethical statement
This was a retrospective study and treatment was performed as per standard plan.
There is no conflict of interest in this paper
NIL.
Financial disclosures
NIL.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Guardian patient relative consents
Obtained.
CRediT authorship contribution statement
Sudam Sadangi: Data curation, Writing – original draft. Hemant Saraiya: Visualization, Investigation. Abhijeet Ashok Salunke: Conceptualization, Methodology, Software. Nandlal Bharwani: Data curation, Writing – Original draft preparation. Keval Patel: Software, Validation. Shivam Pandya: Software, Validation. Vikas Warikoo: Writing – review and editing. Shashank Pandya: Supervision.
Declaration of Competing interest
The authors declare no conflict of interest.
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