Factors, treatments, and outcomes associated with primary soft tissue malignancies of the forearm: A series of 31 cases

Abstract

Background

Primary soft tissue malignancies of the forearm constitute up to 24% of soft tissue extremity malignancies and present a difficult problem when attempting to preserve both life and forearm function. As described by Enneking, recurrence and metastasis are the two largest contributors to morbidity and mortality and therefore, the primary consideration must be to excise the entire tumor. However, since limb salvage is the preferred treatment over amputation in 95% of cases, many physicians elect to perform marginal resections over wide resections in the attempt to increase functional outcomes. Our study aimed to compare recurrence rates and forearm functional outcomes between these groups to better guide clinical decision making.

Questions/purposes

(1) What is the difference in recurrence rates between wide resection of the tumor and marginal resection? (2) Between wide and marginal resection groups, what is the functional difference as measured by MSTS functional outcome scores? The purpose of our study was to answer these two questions and better understand if marginal resection yielded better results compared to wide resection.

Patients and methods

Following IRB approval, we conducted a retrospective case series between 1999 and 2019. Included in the study were patients with a primary malignancy in the predetermined borders of the forearm with a minimum of two-year follow up post-operatively. All patients in the study were operated on by physicians in the Southern California Kaiser Permanente system. Thirty-one patients met criteria for the study. Recurrence rates and metastatic disease was determined through serial history and physical examination, with patients undergoing magnetic resonance (MRI) imaging of the affected area and computed tomography (CT) of the chest every 6 months for the first 2 years, and every 12 months for the following 3 years. MSTS scores were obtained in subsequent follow-ups following the guidelines set by the MSTS scoring system.

Results

Of the 31 patients evaluated, 4 (12.9%) had recurrence and 2 (6.5%) had signs of metastasis. Between the marginal excision and wide excision groups, all 4 recurrences happened in the marginal excision group and none occurred in the wide excision group. In addition, in the pathology report, excisions with 0.1 cm margins or less on any side had 3 instances of recurrence (31%) whereas there was only 1 recurrence (4.8%) outside of this group. MSTS scores for both wide excision and marginal excision were within 1 point with average scores being 26 and 26.9, respectively.

Conclusions

Consistent with the literature, our study found that closer surgical margins lead to higher rates of recurrence due to the increased likelihood of aberrant tumor. However, when looking at functional outcome scores, we found minimal benefit in marginal resections compared to wide resections. The lack of MSTS score difference between both groups highlighted that the perceived benefit of choosing a marginal resection over wide excision may be nominal at best. Therefore, we recommend performing an additional intraoperative resection on narrow margins to reduce the chance of recurrence. Of note, clinical discernment in the form of preserving valuable neurovascular structures such as the median nerve should still be an important consideration.

1. Introduction

Soft tissue sarcomas of the forearm represent 24% of primary malignancies in the upper-limb.⁸ Although rare, forearm sarcomas present a difficult balance between the preservation of life and overall limb function. Tumor recurrence is a strong predictor for future morbidity and mortality and should be the physician's primary consideration.¹⁶ Due to the complex anatomy of the forearm, many valuable structures reside in close proximity to one another and in the same muscular compartments. Therefore, a surgical resection must be done with precision to prevent the recurrence of the tumor while avoiding damaging these structures and still maintaining decent forearm function. Very little research has been done regarding the factors, treatments, or outcomes associated with primary forearm tissue malignancies. These mainly include plastic surgery case reports and case series focusing mainly on reconstruction, and without specificity to the forearm.1, 2, 3, 4, 5, 6, 7 Our study explores the relationship between forearm malignancies, margin of resection, recurrence rate, and functional outcomes. Our goal is to highlight some important considerations that will help guide clinical and surgical practice for forearm sarcomas.

2. Methods and materials

We conducted a retrospective case series of patients in the SCPMG Orthopedic Oncology 37 Database over a twenty-year period of time from 1999 to 2019. Soft tissue sarcoma diagnosis, type, stage, and size were determined in the final pathology report within the Southern California Kaiser Permanente system. All patients with primary forearm malignancies were included in the results of the study. We defined the forearm as the anatomic region between the center of the elbow joint and the center of the wrist joint. The inclusion criteria were patients who had malignancy within the predetermined borders of the forearm, had a primary malignancy, and were treated by a physician in the SCPMG system. There were 31 patients who met criteria for the study.

There is no standard surgical procedure that all physicians followed, however similar practices were implemented. Twenty-nine of the 31 patients were treated with limb sparing surgical intervention and 2 patients had their forearm amputated proximal to the elbow joint. Radiation and chemotherapy were used both preoperative and postoperative to ensure lower recurrence rates. Between the two adjuvant therapies, 23 (74%) were treated with preoperative radiation and 5 (16%) were treated with chemotherapy.

Local disease control and metastatic disease were determined through serial history and physical examination, with patients undergoing magnetic resonance (MRI) imaging of the affected area and computed tomography (CT) of the chest every 6 months for the first 2 years, and every 12 months for the following 3 years. Survival was determined by the number of patients living at the time of the study. To evaluate limb function, we used Musculoskeletal Tumor Society (MSTS) scoring system, an assessment tool that evaluates upper extremity limb function based on six domains scored on a scale of 0–5 with a higher score signifying better function. Included in these criteria are pain, function, emotional acceptance, hand position, dexterity, and lifting ability. Patients were surveyed in subsequent follow-ups to determine overall function. Given the lack of published data in regard to this specific condition, no historical controls were used.

3. Results

Thirty-one cases of primary forearm sarcomas were identified and evaluated for disease control and function. Of the 31 patients, 16 were male and 15 were female with an average age of 51.1 years (range: 21–82). Our patient population had a right dominance with 22 patients experiencing sarcomas on the right side and 9 on the left side, with the volar compartment being the most common. The most frequent sarcoma was synovial-type with 8 patients, followed by the pleomorphic type with 4 patients. There were 4 instances of recurrence, with an average time between surgery and recurrence being 33 months (range 15–64 months). Three of the four cases of recurrence were initially treated surgically (biopsied or resected) by surgeons not specifically trained in orthopedic oncology. Of these 4 recurrences, 1 developed metastatic disease.

Of the 31 primary sarcomas, 19 were deep and 12 were subcutaneous with the average size being 5.13 cm (range: 1.0–16 cm). Both the deep tumors and subcutaneous tumors had two instances of recurrence; however, deep sarcomas contributed to all 3 metastases seen in the population. Looking at the margin of excision, there were 19 wide resections of the forearm, 10 focally marginal, and 2 radical resections. Of those, 4 out of 10 (40%) focally marginal excisions had recurrence whereas the other two groups had none. This showed a statistically significant (p = .0035) increase in recurrence with focally marginal resections versus true wide margins. During the final pathology report, exact margins were identified and measured. There were 10 patients who had tumor cell margins that were deemed positive or less than 0.1 cm, and the remaining 21 were negative for tumor. Of these, 3 out of the 10 margins less than 0.1 cm had recurrence (30%) and only 1 of the 21 (4.8%) negative margin samples had recurrence.

Between the 31 patients, 14 were operated on by surgeons not trained in orthopedic oncology and 17 were treated by trained orthopedic oncologists. The former group had 3 instances of recurrence whereas the oncology-trained orthopedics had 1 recurrent tumor. The average follow up was 67 months (range 8–121 months), and no patients were lost to follow up. Twenty-seven of the 31 patients had no evidence of disease at latest follow-up and 28 were still alive at the time of the study.

Patients were surveyed in subsequent follow-ups to determine overall function and we found that the average MSTS score was 25 out of 30 or 83% of normal function (range 4–30). Those without amputations had improved mean functional scores compared to those with amputations (6.5 vs 26.2). Deep tumors had lower MSTS scores (23.4) when compared to subcutaneous tumors (27.4). Of note, there was less than a one point difference in MSTS scores between wide resections and focally marginal resections, 26.0 and 26.9 respectively (Table 1, Table 2, Table 3, Table 4, Table 5).

Table 1.

Primary forearm malignancy diagnosis.

Sarcoma Type	Number	Percentage
Synovial Sarcoma	8	26
Malignant Fibrous Histiocytoma	4	13
Pleomorphic Sarcoma	4	13
Leiomyosarcoma	3	10
Myxoid Liposarcoma	3	10
Epithelioid Sarcoma	2	6
Fibromyxoid Sarcoma	2	6
Melanoma	1	3
Myxofibrosarcoma	1	3
Rhabdomyosarcoma	1	3
Round Cell Liposarcoma	1	3
Migration Inhibitory Factor (MIF) Sarcoma	1	3
Totals	31	100

Table 2.

Primary forearm malignancy location.

Location	Number	Percentage
Compartment
Volar	20	65
Dorsal	8	26
Volar/Dorsal	3	10
Depth
Subcutaneous	12	39
Deep	19	61
Location
Proximal	6	19
Middle	8	26
Distal	17	55

Table 3.

Initial treatments associated with forearm malignancy and recurrence rates.

Type of Resection	Number	Percentage
Marginal	10
Wide	19
Radical	2
Adjuvant
Chemotherapy	5	16
Radiation Treatment	23	74

Table 4.

Recurrence rate as a function of resection width.

Resection Width	Total Number (Percentage)	Recurrence Number (Percentage)
<0.1 cm or Positive	10 (32.3)	3 (31)
>0.1 cm or Negative	21 (67.7)	1 (4.8)

Table 5.

Differences in local control with regards to the training of the initial surgeon.

Surgery Specialty	Number of Recurrence (Percentage)	MSTS Score
Orthopedic Oncology Training	1/17 (5.9)	26.46*
No Orthopedic Oncology Training	3/14 (21.4)	26.07

* Amputations were removed from consideration.

4. Discussion

4.1. Background

Primary forearm sarcomas comprise 24% of upper extremity malignancies and present a unique challenge to orthopedic surgeons. Given the complexity and relative proximity of forearm structures to each other, any surgical intervention presents a high chance of disrupting future forearm function.^17,18 This includes compromised grip strength, extensor and flexor function, and sensory signaling. Balancing these two priorities, decreasing recurrence rates while preserving function, is the main target goal for physicians operating on these malignancies. Therefore, we reviewed our oncologic database in order to determine the function, disease control, and survival associated with these conditions, especially in relation to their associated factors and treatments.

4.2. Surgical margins Predicting recurrence

One of the greatest predictive markers for recurrence is surgical margin, with positive margins having an increased incidence of recurrence.^8,9,11,12,14 Having closer surgical margins increases the likelihood that aberrant tumor remains behind after surgical excision.¹⁷ Focally marginal margins had a statistically significant increase in recurrence rate when compared to true wide margins. Hasley et al. found that focal margins had similar rates of recurrence to positive margins and therefore we defined any margin of 0.1 cm or less as positive to see if there was any relationship between postoperative margin and local recurrence.¹² Looking at postoperative margins of less than 0.1 cm we found that 3 of the 4 local recurrences had surgical margins less than 0.1 cm. This is consistent with the general consensus that focal margins or positive margins correlate strongly with local recurrence, although there is some debate.^8,9,11,13, 14, 15

4.3. Surgical margin width Predicting functional outcomes

On the other hand, when looking at MSTS scores, there was no significant decrease in forearm function between focally marginal and true wide resections (26.9 vs 26.0, respectively). The perceived benefit of focally marginal resections on forearm function was minimal at best. This highlights a potential disparity between beliefs about how much loss of forearm function there is with wider resections. It should be noted that some of the close surgical margins are in order to preserve important forearm structures such as the median nerve or muscle compartment and are therefore necessary narrow margins. Our team suggests increasing intraoperative resection if the pathology report determines less than 0.1 cm margin on one side while not compromising clinical discernment. Finding the delicate balance between decreasing recurrence rates and reasonable function remains a widely discussed topic and our study aims to contribute to the ongoing discussion.

4.4. Location of tumor Predicting rates of recurrence and metastasis

Of the 31 total sarcomas, there were 19 deep tumors and 12 subcutaneous tumors. When comparing deep tumors versus subcutaneous tumors, there was no significant finding for recurrence as both had two instances thereof. As expected, larger tumors contributed to lower MSTS scores because they required larger overall surgical invasion and compartment disruption. Therefore, in highly malignant tumors, earlier diagnosis and surgery can have a positive impact on long-term forearm function. Deep tumors had all 3 instances of metastasis and 15.8% of all the deep tumors resulted in metastasis, with the most common location being the lung. Since metastasis is one of the greatest predictors of 5-year survival, it is of particular concern for surgeons to determine tumor size and malignancy in order for an early diagnosis and removal.^10,12,14,15 Our study provides potential reasons for treating larger tumors more aggressively with chemotherapy to decrease the opportunity for tumors to have distant metastasis.

4.5. Surgeon training on outcomes

Given the difficulty in differentiating malignant from benign tumors at presentation, many of the patients in our study were initially treated by non-oncologically trained orthopedics. Recurrence rates were decreased among oncologically trained orthopedics when compared to non-oncologically trained orthopedics (1 case out of 17 compared to 3 cases out of 14 respectively), likely due to better understanding of the chemotherapy and radiation techniques as well as importance of resection width as a function of care. MSTS scores did not change between groups suggesting the surgical technique is consistent between groups in preserving important structures. There is strong evidence of the value of radiation and chemotherapy treatment as a way to decrease metastatic disease and if properly diagnosed, patients should be referred to an orthopedic surgeon trained in oncology to ensure the best disease control outcome.

The goal of our research is to highlight relationships between local recurrence rates and MSTS scores to help guide care. Since the forearm is anatomically complex, physicians must be careful when surgically resecting soft tissue malignancies of the forearm to avoid risking recurrence while ensuring adequate forearm function for daily use.

4.6. Limitations

The main limitation of our research is due to sample size in which 31 patients qualified for the study. However, since primary forearm sarcomas are very rare, especially constrained to one anatomical location, this particular data set highlights important findings. Although a low number of patients decreases the power of the study, general trends and conclusions were supported by outside literature reviews and our findings can be used to help guide patient care.

Funding

No industry funding was received in association with this study.

Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and informed consent for participation in the study was obtained.