Incidence and Severity of Lymphoedema following Limb Salvage of Extremity Soft Tissue SarcomaClinical Study
Volume 2011 (2011), Article ID 289673, 6 pages
Daniel Friedmann,1 Jay S. Wunder,2,3 Peter Ferguson,2,3 Brian O'Sullivan,4 David Roberge,5 Charles Catton,4 Carolyn Freeman,5 Neil Saran,1 and Robert E. Turcotte1
1Division of Orthopedic Surgery, McGill University Health Centre, Montreal, QC, H3G 1A4, Canada
2Musculoskeletal Oncology Unit Division of Orthopedic Surgery, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada
3Department of Surgical Oncology, Princess Margaret Hospital, Toronto, ON, M5G 2C4, Canada
4Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, M5S 3S2, Canada
5Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, H3G 1A4, Canada
Received 17 August 2011; Revised 28 September 2011; Accepted 28 September 2011
Academic Editor: Luca Sangiorgi
2011 Daniel Friedmann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background and Purpose. Lymphoedema is a serious complication following limb salvage for extremity soft tissue sarcomas (STSs) for which little is known. We aimed to evaluate its incidence, its, severity and its associated risk factors. Material and Method. Patient and tumor characteristics, treatment modalities and complications and functional outcomes (MSTS 1987, TESS), and lymphoedema severity (Stern) were all collected from prospective databases. Charts were retrospectively abstracted for BMI and comorbidities. Results. There were 289 patients (158 males). Mean age was 53 (16–88). Followup ranged between 12 and 60 months with an average of 35 and a median of 36 months. Mean BMI was 27.4 (15.8–52.1). 72% had lower extremity tumors and 38% upper extremity. Mean tumor size was 8.1 cm (1.0–35.6 cm). 27% had no adjuvant radiation, 62% had 50 Gy, and 11% received 66 Gy. The incidence of lymphoedema was 28.8% (206 none, 58 mild, 22 moderate, 3 severe, and 0 very severe). Mean MSTS score was 32 (11–35) and TESS was 89.4 (32.4–100). Radiation dose was significantly correlated with tumor Radiation dose was significantly correlated with tumor size less then 5cm and TESS score, but not MSTS score (P=0.090) Only tumor s i z e > 5 cm and depth were found to be independent predictors of significant lymphoedema. Conclusion. Nine percent of STS patients in our cohort developed significant (g r a d e ≥ 2
) lymphoedema. Tumor s i z e > 5 cm and deep tumors were associated with an increased occurrence of lymphoedema but not radiation dosage.
Soft tissue sarcomas (STSs) comprise a group of rare malignant tumors occurring most commonly in the extremities [1, 2]. Preferred treatment for patients with STS is limb preservation surgery usually in combination with adjuvant preoperative or postoperative radiation therapy [1, 3–7]. This treatment carries a significant risk of functional disability and reduced quality of life [6, 8], and up to 50% of patients live with significant long-term disability .
Studies that have compared preoperative to postoperative external-beam radiotherapy (EBRT) as part of limb sparing surgery for patients with extremity STS have shown that, while preoperative EBRT allows the use of lower doses and smaller treatment fields, such an approach is associated with increased risk of acute wound healing complications [3, 6, 10]. Postoperative EBRT typically requires the use of higher radiation doses and larger target volumes and is associated with increased late radiation-related morbidity [3, 11]. One important complication which has been given very limited attention thus far is secondary lymphoedema.
Lymphoedema is swelling that generally occurs in the limbs, or less commonly in visceral and axial structures, due to an accumulation of protein-rich lymph fluid in the interstitial tissues [12, 13]. In patients with STS, lymphatic injury may result from surgical disruption of lymph nodes, lymphatic or major blood vessels. Alternatively, the lymphatic system may be damaged by radiotherapy leading to fibrosis and compromised lymph transport . Patients presenting with lymphoedema secondary to treatment for STS are prone to developing recurrent infections and skin changes such as hyperkeratosis and papillomatosis . Beyond the physical symptoms and signs, lymphoedema may also be associated with significant psychological and functional morbidities such as poor body image leading to anxiety and depression .
Lymphoedema in the upper extremities has been studied extensively in the breast cancer population. The frequency of occurrence is extremely variable ranging from 3% to 83%, although generally accepted to be approximately 30% [16–19]. Several predisposing factors have been identified, most importantly axillary surgery (lymph node dissection) and axillary radiotherapy [15, 17, 19, 20]. Other factors which may also influence the risk of lymphoedema in the breast cancer population include the stage at diagnosis, systemic therapies (chemotherapy or hormonal therapy), age, body mass index, hypertension, history of infection, and pretreatment education regarding lymphoedema and preventive self-care activities [2, 15, 17, 21, 22].
Few studies have addressed the question of lymphoedema in patients with STS, which occurs most commonly in the lower extremities [2, 4, 8]. Previous soft tissue sarcoma series reported an incidence of lymphoedema of 30% while others recorded significant lymphoedema (grade ≥2) in 19% [4, 8, 18, 23]. High biologically effective dose (BED), radiation field length >35 cm and lower extremity location were identified as positive risk factors for the development of chronic oedema.
The objective of this study was to identify the incidence and the severity of lymphoedema, and to evaluate the potential risk factors in patients with extremity soft tissue sarcoma who have undergone limb preservation surgery with or without adjuvant external beam radiotherapy.
Our prospective tumor database served to identify patients who had undergone surgical management of extremity STS at the Montreal General Hospital, Montreal, Quebec, and the Mount Sinai Hospital, Toronto, Ontario, between 2000 and 2007. All patients selected for inclusion in this study had prospective collection of lymphoedema severity rating at an interval of at least 1 year following treatment. Lymphoedema severity was evaluated using Stern’s Rating Scale for Edema. Stern’s scale is a subjective, physician-rated measure with scores ranging from 0 to 4 (Table 1) . Functional outcomes were assessed using the Musculoskeletal Tumor Society Rating scale (MSTS) and the Toronto Extremity Salvage Score (TESS). The MSTS is a clinician-rated scale which evaluates pain, joint range of motion, strength, joint stability, joint deformity, overall function, and general acceptance of the treatment; the score ranges from 0 to 35 . The TESS is a patient-rated measure developed specifically for patients undergoing limb salvage surgery for bone and soft tissue sarcomas which evaluates difficulty performing daily activities . All three outcomes were collected simultaneously at a mean interval of 35 months from treatment (range 12–60). Patients’ demographics, tumor characteristics, and treatment-related variables were prospectively collected. Charts were also retrospectively abstracted for body mass index (BMI) and to identify medical comorbidities including the occurrence of thrombophlebitis.
The association between size of the tumor and the likelihood of having significant lymphoedema (grade 2 or 3) was modeled using logistic regression. Tumor size was categorized as small or large with large representing tumors 5 cm or greater, and the small category was used as the reference for the analysis. The following variables were included as independent variables to obtain adjusted effects: age was a continuous variable, and not allowed, BMI, upper versus lower extremity, whether or not a lymph node dissection was performed, radiation, and smoking were categorical variables with male not allowed, BMI <30 kg/m2, upper extremity, no node dissection, no radiation, and nonsmoker coded to serve as reference categories. Initially, depth of the tumor was also included as a variable; however, seeing as there were no cases of lymphoedema in the superficial group, this had to be removed from the analysis. Regression coefficients were exponentiated to determine the odds ratio (OR) of significant lymphoedema compared to nonsignificant lymphoedema for a large tumor as compared to a small tumor. The log-likelihood ratio test was used to assess the significance of the association fitted by the model, and individual regression estimates are tested by Wald statistics for significance by assessing the null hypothesis that the regression estimates are equal to zero. A P-value of 0.05 was used as the cut-off for significance. All statistical analyses were performed using SPSS 19 (IBM, Armonk, NY).
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