STS of the forearm is rare and characterized by a high likelihood of unplanned excision, high rate of local recurrence (7–38%), and distant metastases (13–24%)9, 11. However, patient characteristics, factors associated with the receipt of unplanned versus planned excision, functional outcomes, and oncological outcomes have not been fully investigated. We found that 41% of forearm STS were referred to our institution following an unplanned excision, which was characterized by a tumor size <2 cm. The median MSTS score was 28, which was influenced only by bone resection or major nerve palsy but not by reconstructive procedures (the use of flap and tendon reconstruction). We found that the 5-year LRFS, MFS, and OS rates were 86%, 77%, and 78%, respectively. The histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS, while age ≥65 years was associated with an increased risk of OS.
Some authors reported a high percentage of unplanned excision without preoperative suspicion of malignancy in 25–45%9, 11. In line with these reports, 41% of our patients were referred for an unplanned excision to manage their forearm STS. Furthermore, most unplanned excisions of forearm STS were probably performed without suspicion of malignancy, as only half of them received preoperative MRI. According to Baroudi et al., the characteristics of tumors with unplanned or planned excision differ in size (<4 cm in 81% and 23%, respectively) and depth (superficial in 57% and 23%, respectively) in patients with forearm STS11. We found that tumor size ≥2 cm was the only factor associated with the receipt of unplanned excision (P = 0.02). All patients with tumors <2 cm underwent unplanned excision, whereas 10/30 patients with tumors ≥2 cm underwent unplanned excision. The effect of unplanned excision on survival remains controversial. Potter et al. reported that the 5-year LRFS was higher in the unplanned excision group (63.7%) than in the planned excision group (89.7%) (P < 0.0001) for patients with extremity and trunk STS13. Baroudi et al. reported that there was no difference in LRFS, MFS, and OS in patients with unplanned excision and planned excision for patients with forearm sarcoma11. We also found no difference in LRFS, MFS, and OS between patients with unplanned excision and planned excision. This can be explained by the tumors with unplanned excision being less aggressive (lower grade and earlier stage than tumors with planned excision), which could compensate the inadvertent treatment. Although the prognostic significance of unplanned excision should be further investigated, one should be careful in treating soft-tissue masses through conducting a comprehensive history taking and physical examination, requesting imaging tests, and referring these patients to a tertiary sarcoma center when they are suspected for a sarcoma.
The goal of forearm STS treatment is to obtain wide resection margins of the primary tumor, while preserving upper limb function. However, it becomes challenging because of the complex anatomy and limited tissue volume of the forearm. Postoperative loss of tissues requires reconstruction of combined tissues, including the skin, tendons, nerves, vessels, bones, and joints. To achieve optimal oncological and functional outcomes, treatment strategies, including adjuvant treatments, should be defined by a multidisciplinary team including an oncological surgeon, hand surgeon, and plastic surgeon. These reconstructions greatly affect the postoperative functional outcome. Few studies have reported the functional outcomes of forearm STS. Muramatsu et al. reported median MSTS scores of 29.5 in eight patients who received microvascular reconstruction (5 free flaps)9. In the study by Bray et al., the functional outcomes were better in patients with forearm STS than in those with STS in the hand and wrist, with a mean TESS of 94 versus 887. Certainly, it is difficult to accurately compare the functional outcomes of forearm STS with variable extents of excision, reconstruction, and functional scores (MSTS and TESS). However, these reports showed the possibility of good to excellent functional outcomes of forearm sarcoma, regardless of the receipt of adjuvant therapy or microvascular reconstruction. Similar to these reports, we found a median MSTS score of 28. Furthermore, we found that bone resection or major nerve palsy had significant effects on the MSTS score in forearm STS.
In the case of skin defects, which cannot be covered by split thickness skin graft (STSG), local pedicled or perforating flaps can be utilized16, 17. However, they can increase the risk of cross-contamination. Thus, we usually use a free flap, commonly the anterolateral thigh (ALT). Other flaps such as latissimus dorsi (LD) flap, superficial circumflex iliac artery perforator (SCIP), abdominal, and inguinal are alternative candidates. Kang et al. reported that the flap reconstruction group had a lower MSTS score and higher wound complication rate but had better local control than those in the primary closure group in patients with STS of the upper extremity18. Others found that there was no significant difference in complication rate and functional outcomes between the pedicled and free flap groups in the upper extremity19, 20. In this study, we first found equivalent limb function measured by MSTS with or without the use of a free flap in patients with forearm STS. Although partial necrosis was seen in two patients, they healed without any complication. Thus, the free flap is a safe and reliable procedure without impairing forearm function and minimal complications.
To the best of our knowledge, only one report has assessed the functional outcomes of forearm sarcoma with tendon reconstruction. Muramatsu et al. reported four cases with defects of the flexor or extensor forearm muscle after tumor resection that received functional neurovascular musculocutaneous flaps (free re-innervated transfer of gracilis or LD) to reconstruct finger flexors and extensors9. Reinnervation of the transferred muscle was obtained in all cases, and functional outcomes were evaluated as good to excellent, with a median MSTS score of 28 (20–30). We usually reconstruct flexors, extensors, or both muscle groups (flexor digitorum profundus [FDP], extensor digitorum [ED], flexor pollicis longus [FPL], and extensor pollicis longus [EPL]) using tendon autografts or tendon transfer techniques. We reconstructed the tendon in eight patients who underwent resection of flexors and/or extensors (FDP, ED, FPL, and EPL). We found equivalent limb function measured by the MSTS in patients with or without tendon reconstruction, suggesting that the function of the forearm can be compensated by tendon reconstruction.
We found that bone resection or neurological disturbance (major nerve resection or paralysis) led to major loss of function, as median MSTS scores in patients with and without these factors were 24 (18–25) and 29 (18–30), respectively (P < .001). In this study, three patients underwent ulnar resection, and among them, two patients lost their distal radioulnar joint (DRUJ). Although one patient received free vascularized fibular graft (FVFG) for the defect of the diaphysis of the ulna, this resulted in insufficient function. Preserving the major nerves is extremely important in the forearm, as sacrificing a major nerve leads to a major loss of function. Careful preoperative planning and adjuvant treatment may be necessary for preserving the major nerves. We performed epineural microsurgical dissection called in situ preparation (ISP) to avoid complete resection of major nerves when the tumor was located very close to them21. Invasion of nerve fibers by the tumor is rare, but the nerves can be preserved in most cases through this procedure. However, segmental resection cannot be avoided when the nerves are completely entrapped within the tumor. A nerve defect can be reconstructed using an interposition graft (sural nerve), distal nerve transfer, and vascularized nerve graft. However, the recovery of function is unpredictable; furthermore, its role in the reconstruction of major nerve defects has not yet been recognized5. In this study, postoperative neurological disturbance was observed in three patients without recovery, which led to severe hand dysfunction.
To the best of our knowledge, only one report has assessed survival and its associated risk factors in patients with forearm STS11. Baroudi et al. reported a local recurrence rate of 7% and a 5-year LRFS rate of 94%11. In this study, the local recurrence rate was 18%, while the 5-year LRFS rate was 86%. The histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS. Myxofibrosarcoma has a locally infiltrative behavior and is associated with a high local recurrence rate of 24–44%22–24. Dadrass et al. reported that although positive resection margins were associated with local recurrence of myxofibrosarcoma, negative margins also resulted in a relatively high rate of local recurrence (13%) compared to other soft tissue sarcoma subtypes22. In line with previous studies, a high rate of local recurrence was observed in this study; 4/10 myxofibrosarcoma patients experienced local recurrence, although all of them had achieved R0 margins. The 5-year LRFS rates of myxofibrosarcoma and others were 42% and 85%, respectively (P = 0.047). With the small number of patients in this series, we could not show an association between local recurrence and resection margin or the use of RT. Although wide resection margins were presumed to result in good local control of forearm STS, no relationship between local recurrence and surgical margins was confirmed in this study. Baroudi et al. also reported no relationship between local recurrence and surgical margins in forearm STS11. Thus, the utility of surgical margins for local control of forearm STS should be investigated in a larger study. Locally aggressive STS, which makes limb-salvage difficult to achieve, may benefit from RT to avoid amputation in some cases. The role of RT in the treatment of extremity STS has been defined by two randomized clinical trials: RT reduced the risk of local recurrence in patients with high-grade tumors who had positive surgical margins25, 26. Its efficacy in local control does not differ from whether it is utilized before or after surgery, although there is a risk of postoperative complications with neoadjuvant RT25, 26. The role of RT in the treatment of forearm STS has been previously investigated. Bray et al. reported local recurrence in 3/13 patients (two malignant fibrous tumors and one epithelioid sarcoma) who received neoadjuvant RT and tumor resection with negative margin for forearm STS7. In this study, none of the seven patients who received postoperative RT had local recurrence. Thus, the role of RT in the local control of forearm STS should be investigated further. Our treatment strategy for forearm STS is to perform R0 resection and use RT when the resection margins prove to be R1 or R2 because of the close proximity of the tumor to the major nerves or vessels.
Baroudi et al. reported a 5-year MFS rate of 74% and that the extra-compartment site was associated with a poor prognosis11. In this study, the 5-year MFS rate was 77%. Distant metastases were found in three patients upon initial presentation and in eight patients throughout the follow-up period. Among them, nine patients had lung metastases, with four undergoing radical pulmonary metastasectomy. Two patients remained disease-free by the last follow-up. Two patients who underwent resection of lymph node metastases continued to be disease-free during follow-up. Thus, radical metastasectomy is recommended in patients with forearm STS, when possible.
Baroud et al. reported a 5-year OS rate of 81% and described that large (>4 cm) and soft tissue reconstruction were associated with a poor prognosis11. In this study, the 5-year OS rate was 77%, while age (≥65 years) was the only factor influencing OS. Among 16 patients aged ≥65 years, seven died, and the 5-year LRFS rate was 60%. On the other hand, one of 18 patients aged <65 years died; thus, the 5-year OS rate was 94%. The negative impact of older age on the prognosis of patients with STS has been discussed in several reports27, 28. Hoven-Gondrie et al. reported that patients >65 years were more likely to have an advanced-stage and high-grade STS28. They reported that the proportion of patients who received no treatment increased with age, which was significantly associated with relative 5-year survival: 72.7% in younger patients and 43.8% in the elderly (cut-off: 85 years). In line with previous reports, we found high-grade sarcomas and less aggressive treatment in older patients than in younger patients, which would lead to lower OS in older patients than in younger patients. The efficacy of adjuvant chemotherapy with a combination of doxorubicin and ifosfamide was demonstrated in a meta-analysis29. Adjuvant chemotherapy has shown significant improvement in DFS and significantly prolonged OS, with the risk reduction improved to 11% for death and 12% for recurrence29. In this study, there was a trend toward superior OS in patients receiving chemotherapy, although we did not find a significant association between chemotherapy and OS. As other factors may influence this observation, larger studies are needed to confirm a possible association.
This study has several limitations. First, since forearm sarcoma is a rare malignancy, the sample size was small, with only 34 patients included; this limited our ability to identify factors associated with local recurrence and survival. Furthermore, some factors we explored were not necessarily associated with poor survival, and these factors may be important if conducted with a larger series. Second, wide resection was not performed in all patients, because some tumors close to major nerves and vessels were excised with R1 margins; this could have influenced survival rates. However, the sample size was likely insufficient to support this. Third, we investigated the function only by MSTS since we did not use other methods, such as TESS or disability of the arm, shoulder, and hand in all patients. We also did not investigate the grip power or other functions of the fingers. Finally, there may have been selection bias in our application of RT; we usually utilize RT in patients with surgical margins of R1 because of the close proximity of the tumor to major nerves or vessels. However, RT can influence the outcomes of local recurrence.
In conclusion, physicians should be careful in history taking and physical examination, requesting appropriate imaging studies, and referring them to a tertiary sarcoma center when they are suspected to have sarcomas. Resection with wide margins for the whole tumor is preferable; furthermore, RT should be utilized when marginal resection is performed because of the close proximity of the tumor to the major nerves or vessels. Soft tissue reconstruction using tendons can compensate for function, although bone resection and major nerve disturbances may aggravate the condition. The clinical behavior of forearm STS is relatively aggressive. Careful attention during follow-up is important, especially in patients with myxofibrosarcoma, to aid local control. Further studies based on a larger patient cohort would clarify the role of RT and surgical margins in this rare form of malignancy.