Outcome Following Limb Salvage Surgery and External Beam Radiotherapy for High Grade Soft Tissue Sarcomas of the Groin and Axilla Rapin Phimolsarnti M.D. Anthony M. Griffin MSc Peter C. Ferguson MD FRCSC Charles N. Catton MD FRCPC Peter W. Chung, MD FRCSC Robert S. Bell MD FRCSC Jay S. Wunder MD FRCSC Brian O’Sullivan MD FRCPC Musculoskeletal Oncology Unit, Mount Sinai Hospital, University of Toronto. Good afternoon chairman, co-chairman ladies and gentlemen. Today it is my pleasure to present a study from the Musculoskeletal Oncology Unit, University of Toronto. In the topic the “outcome following limb salvage surgery and external beam radiation for the high grade soft tissue sarcomas of the groin and axilla.

Introduction High grade sarcoma usually treated with combination of limb salvage surgery and radiation ± chemotherapy. Low rates of local recurrence Impact on overall survival? It has been known that, for a high grade soft-tissue sarcoma, the treatment consist of multimodalities approach from Surgical oncologist (or orthopaedic oncologist), radiation oncologist and medical oncologist to achieve the best possible outcome. This results in a fairly low number of local recurrence in extremity sarcomas. However, prospective studies available still unable to show any direct correlation of the local recurrence to the survival of patients.

Introduction Previous study: soft tissue sarcoma located in the central area which included axilla and groin tumors had less favorable local control compared to more distal anatomic sites when treated with surgery and adjuvant brachytherapy. External beam radiation therapy ? In the previous study regarding to the influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma from Memorial Sloan Kettering, the soft tissue located in the central area seemed to have less favorable local control compare to more distal anatomic sites when treated with surgery and adjuvant brachytherapy Alektiar Ann Surg Oncol 2002

Purpose of the study To determine the outcome in terms of local control and complications in the area of the central flexor fossa (groin and axilla) in our institution treated with external beam radiation therapy and limb sparing surgery. However, the outcome in these area after external beam radiation haven’t been clearly addressed. Therefore, we would like to assess the outcome in terms of Local Recurrence and Complications in the area of central flexor fossa (groin and axilla) treated in our institution after the treatment with External Beam Radiation Therapy and the Limb sparing surgery.

Materials and Methods Review of prospectively collected database Surgery between 1989-2002 Surgery- Mount Sinai Hospital. Radiation Therapy- Princess Margaret Hospital. In this study, we reviewed the database collected prospectively from 1989 to 2002. In all of the cases, the surgery were performed at the Mount Sinai hospital while the radiation therapy were performed at the Princess Margaret Hospital.

Materials and Methods Inclusion criteria: Intermediate to high grade soft-tissue sarcoma of the extremity Treated with limb sparing surgery Pre- or post operative radiation therapy Our selection criteria was any primary intermediate to high grade soft tissue sarcoma of the extremities that had been treated with Limb Sparing Surgery with pre or post operative radiation therapy

Materials and Methods Exclusion criteria. Metastasis at presentation Prior radiotherapy Adjuvant chemotherapy We excluded cases that had metastasis at presentation, had received any prior radiotherapy, or had received any chemotherapy.

Materials and Methods Surgical aspect 3 musculoskeletal oncologists (RSB, JSW, PCF) all performed at MSH Surgical resections were attempted to achieved 2cm margins Exception Natural boundary to tumor invasion (fascia, periosteam) Close to but not fixed to the tumor mass All the Limb sparing surgery were done at Mount Sinai Hospital by one of three Musculoskeletal Oncologists. The surgical resection was attempted to achieved 2 cm. margins. However, the closer margin was accepted if there is a natural boundary (fascia, periosteum, bone) that close to but not fixed to the tumor mass

Materials and Methods Radiation Therapy Pre-op or Post-op 3 radiation oncologist (CNC, PWC and BOS) All performed at Princess Margaret Hospital Pre-op or Post-op Radiation dose 50 Gy for pre-op RT 60-66 Gy for post-op RT Regarding to the radiation therapy, Our patients received either pre operative or post operative radiation therapy with higher dose on post operative protocol.

Materials and Methods Follow up: Calculated from the time of definite surgery to last follow up Local recurrence Physical Exam, MRI Distant Metastasis Chest x-ray, CT scan Complications Wound complications, infection, fracture The follow up time was calculated from the time of the definite surgery. The local recurrence was detected by either physical examination or MRI and distant metastasis was detected by either chest x-ray or CT scan of the lung.

Material and Methods Statistical Analysis Survival rate: Kaplan-Meier Survival curve comparison: Log-rank test Association between variables: Chi-square method Independent prognostic factors: Cox-multivariate analysis We use the statistical methods as shown.

Results 560 adult patients who met the criteria 418 lower, 142 upper Median F/U 52 months 28 cases of tumor located in groin area 16 cases of tumor located in the axilla area

Results There was no difference regarding to the distribution of depth, grade, gender, prior surgery, surgical margin, type of radiotherapy between the central group (axilla and groin) and the more distal group

Results 5 years local recurrence free survival of the entire group = 90.9% 5 years local recurrence free survival of the groin and the axilla group = 90.6% There were no significant difference between two groups (p>0.05)

This is the overall survival of the entire group which it has been shown that the

Results Cox-multivariate analysis Margin, depth, prior “unplanned” excision and anatomical site. Only a positive surgical margin is a significant factor for the local recurrence 5 yr LR-free survival with Negative margin = 93.8% Positive margin = 78.2% (p<0.00001)

Complications 22 (50%) patients in the central location group had complications (wound 15, infection 4, fracture 1) 149 (28%) from 516 patients in the non-central group had complications (wound 108, infection 17, fracture 12)

Discussion Eilber FC et al (Surg Oncol 1999) 1974-1998 UCLA medical center 68 patients with high grade soft-tissue sarcoma of flexor fossae (popliteal, groin, cubital, axilla) Pre-op chemotherapy (Adriamycin, Ifosfamide) and radiation therapy Achieved local control in 89%

Discussion Alektiar et al (Ann Surg Oncol 2002): Memorial Sloan Kettering 1982-1997 202 patients (25 in the central area) High grade soft-tissue tumor Surgical excision with adjuvant brachytherapy 5-yr Local control rate in the central area was lower than other sites (57% versus 88%)

Discussion Alektiar et al: 5-yr local control rate in the central area is lower than other sites Current study- no difference in local control rate between the central area and more distal sites (90.6% versus 90.9%) However, the complications are higher in the groin and axilla group (p=0.003) From Previous study by Dr. Alektiar, the local control

Conclusion An axillary or groin location of an intermediate and high grade sarcoma didn’t confer any greater risk for local recurrence as compared to more distal lesions. However, there are greater risk of complication associate with external beam radiation in the groin or axillary area compare to more distal lesion Positive margin remains the major risk factor for Local recurrence rate.

Thank you for your attention