Study population and treatment modalities.
From 1995 to 2017, 40 consecutive histologically proven cases of PVNS were found. Seven cases were excluded due to localized PVNS, and nine were excluded due to origins other than knee joint. Twenty-four patients with diffuse PVNS of knee were included, including 13 women and 11 men. The mean age was 40.4 years (range 19-65 years) (Table 1). Of the 24 patients, the majority were treatment-naïve without previous surgical interventions or RT before the index operations to the affected knee. Only one patient had undergone a previous synovectomy.
Twelve patients underwent open synovectomy and received adjuvant RT (OP+RT), seven underwent open synovectomy alone (OP), two underwent arthroscopic synovectomy and received postoperative RT (AS+RT), and three underwent arthroscopic synovectomy alone (AS).
After synovectomy, 58.3% (14/24) of the patients received adjuvant external-beam RT by three-dimensional (3D) conformal or intensity-modulated radiation therapy (IMRT) technique. The median RT dose delivered was 36 Gy (range, 20-40 Gy) with a median of 16 fractions (range, 10-20 fractions). Most patients (n=11) received 30-36 Gy in 14-18 fractions (Table 2). No patient was treated with intra-articular yttrium-90. No patient suffered from wound breakdown, and there was no episode of deep infection. There was also no case of severe skin reaction (skin reaction greater than grade 2 on the RTOG grading system).
Incisions of open synovectomy
In our hospital, posterior synovectomy was not a routine procedure for diffused PVNS. The choice between treatment of open anterior with or without posterior approaches of synovectomy was mainly based on the pre-operative MRI. The combined posterior approach of synovectomy was adapted when the anterior or posterior cruciate ligament was extensively invaded by PVNS.
Among the study cohort, there were 11 cases receiving combined open anterior and posterior synovectomies. There was no case of combined anterior arthroscopic and posterior open synovectomy.
After a median follow-up of 6 years (range 2-15 years), the overall local recurrence rate was 41.7% (10 of 24 patients), including 6 demonstrating progression with gross disease on post-treatment MRI and 5 receiving re-operation of the affected knee with documented recurrences. Comparing the outcomes among treatment modalities, there was a significantly higher local control rate with open synovectomy and adjuvant RT (Supplementary Table 1). When focusing on those receiving open synovectomy, the local control benefit of adjuvant RT was still apparent, with a local recurrence rate of 8.3% in the OP+RT group versus 57.1% in the OP group (p=0.038) (Table 3).
With moderate dose and the use of 3D conformal and IMRT technique, the acute and long-term toxicities of external beam radiotherapy were relatively mild in our study. There was no case of surgical wound breakdown nor deep wound infection recorded in those receiving adjuvant RT. Furthermore, there was no grade 2 or greater long-term skin reaction nor soft tissue edema.
Overall Functional outcomes
Among the 24 cases, 4 patients were excluded from WOMAC score evaluation due to receiving total knee arthroplasty of the affected joints for progressive osteoarthritis after the index treatments, including 3 receiving open synovectomy and 1 arthroscopic synovectomy, all without adjuvant radiotherapy. There were 20 patients with preserved knee joints at recruitment and 19 completed functional outcome measures through phone interviews while 1 refused the interview. Their mean WOMAC score was 88 (range 48-100) (Tables 3-4). After long-term follow-up, neither the total WOMAC score nor stiffness score was significantly different between those who received adjuvant RT and those who did not, in both overall and the open synovectomy group (Table 4, Supplementary Table 1).
Overall, the mean WOMAC score for the 4 patients receiving OP alone was 84. (Table 3.) An extremely poor functional outcome was reported in a 59-year-old female presented (WOMAC score=48). She first received open anterior and posterior synovectomy without adjuvant RT. However, local recurrence was noted and she underwent re-operation once in other hospital. According to the statement of the patient, there are difficulties going up and down the stairs, as well as arising from a sitting position. She also reported persistent joint pain and stiffness at the 5-year post-operative follow-up with a WOMAC stiffness score of 4, WOMAC pain score of 9, and WOMAC physical function score of 35. On the other hand, the mean WOMAC scores of the 6 patients receiving OP+RT was 91.6. (Table 2. and Table 3.) Extremely poor function was not observed.
To analysis the impact of adjuvant RT and disease recurrence on joint function, further analysis was performed, excluding those who received TKA. The proportion of patients with good functional outcomes (WOMAC score >90) was higher among those without recurrent disease (8/12 without recurrent PVNS versus 3/7 for those with recurrent PVNS). However, the correlation between recurrence and poor WOMAC score was not statistically significant (p=0.226). When testing the effect of adjuvant RT, rates for good functional outcomes were 61.5% (8/13) for those receiving adjuvant RT, which was higher than 50% (3/6) for those without adjuvant RT, though no statistically significant difference found. Regressions between the WOMAC score as continuous variable and the dose of adjuvant RT revealed no significant correlation. (Table 2)