Faculty Bibliography

OBJECTIVE:Neoadjuvant chemoradiation (NA-CRT), followed by resection of high-risk soft tissue sarcoma (STS), may offer good disease control and toxicity outcomes. We report on a single institution's modern NA-CRT experience. MATERIALS AND METHODS/METHODS:Delay to surgical resection, resection margin status, extent of necrosis, tumor cell viability, presence of hyalinization, positron emission tomography (PET)/computed tomography data, and treatment toxicities were collected. Using the Kaplan-Meier survival analysis, 5-year overall survival, disease-free survival, distant metastasis-free survival, and local control (LC) were estimated. Clinicopathologic features and PET/computed tomography avidity changes were assessed for their potential predictive impact using the log-rank test. RESULTS:From 2011 to 2018, 37 consecutive cases of localized high-risk STS were identified. Twenty-nine patients underwent ifosfamide-based NA-CRT to a median dose of 50 Gy before en bloc resection. At a median follow-up of 40.3 months, estimated 5-year overall survival was 86.1%, disease-free survival 70.2%, distant metastasis-free survival 75.2%, and LC 86.7%. Following NA-CRT, a median reduction of 54.7% was observed in tumor PET avidity; once resected, median tumor necrosis of 60.0% with no viable tumor cells was detected in 13.8% of the cases. Posttreatment resection margins were negative in all patients, with 27.6% having a margin of ≤1 mm. Delays of over 6 weeks following the end of radiation treatment to surgical resection occurred in 20.7% cases and was suggestive of inferior LC (92.8% vs. 68.6%, P=0.025). CONCLUSIONS:This single-institution series of NA-CRT demonstrates favorable disease control. Delay in surgical resection was associated with inferior LC, a finding that deserves further evaluation in a larger cohort. LEVEL OF EVIDENCE/METHODS:Level III-retrospective cohort study.

Palliative cervical cordotomy can be performed via percutaneous radiofrequency ablation of the lateral C1-2 spinothalamic tract. This rare procedure can be safe, effective, and advantageous in mitigating medically intractable unilateral extremity pain for selected patients with end-stage cancer. This report reviews the indications, techniques, risks, and potential benefits of cordotomy. We describe our recent experience treating 3 patients with CT-guided C1-2 cordotomy and provide the first characterization of spinal cord diffusion MR imaging changes associated with successful cordotomy.

Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare malignancy, especially in adults. Case Presentation. A 40-year-old male presented with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass with no osseous involvement. He underwent surgery for gross total resection of the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of the literature indicated only 45 previously reported cases of spinal epidural extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare clinical entity that should be included in the differential for spinal epidural masses. Its treatment is multidisciplinary but frequently requires surgical intervention due to compressive neurologic symptoms. Gross total resection appears to correlate with improved outcomes.

BACKGROUND: Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand. METHODS: We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment. RESULTS: Twenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24-78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400-800 mg daily. The most common side effect was grade 1-2 LFT elevations; grade 3-4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients. CONCLUSIONS: These data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.

In this issue, Bollling et. al. review the development of treatment of Ewing sarcoma as it evolved over the past 30 years of clinical trials in Europe, largely under the leadership of Heribert Jurgens to whom this review is dedicated. The 44 authors were teachers, colleagues, students and co-investigators of Jurgens. The authors attribute the ability to make progress in the treatment of Ewing sarcoma through the establishment of larger and still larger cooperative studies in order to demonstrate statistically significant advances in the treatment of this rare disease.

Background. Uterine leiomyosarcoma (LMS) is a rare diagnosis, which is seldom cured when it recurs with metastatic disease. We evaluated patients who present with first time recurrence treated surgically to determine prognostic factors associated with long-term survival. Methods. Over a 16-year period, 41 patients were operated on for recurrent uterine sarcoma. Data examined included patient age, date of initial diagnosis, tumor histology, grade at the initial diagnosis, cytopathology changes in tumor activity from the initial diagnosis, residual tumor after all operations, use of adjuvant therapy, dates and sites of all recurrences, and disease status at last followup. Results. 24 patients were operated for first recurrence of metastatic uterine LMS. Complete tumor resection with histologic negative margins was achieved in 16 (67%) patients. Overall survival was significantly affected by the FIGO stage at the time of the initial diagnosis, the ability to obtain complete tumor resection at the time of surgery for first time recurrent disease, single tumor recurrence, and recurrence greater than 12 months from the time of the initial diagnosis. Median disease-free survival was 14 months and overall survival was 27 months. Conclusion. Our findings suggest that stage 1 at the time of initial diagnosis, recurrence greater than 12 months, isolated tumor recurrence, and the ability to remove ability to perform complete tumor resection at the time of the first recurrence can afford improved survival in selected patientsat the time of the first recurrence can afford improved survival in selected patients.

BACKGROUND: Diaphragmatic sarcomas are extremely rare and mostly described in children. We present the case of an adult with rhabdomyosarcoma of the diaphragm. METHODS: We performed a literature review, highlighted possible diagnostic pitfalls, and discussed multidisciplinary treatment options.

Purpose: Primary and metastatic sarcoma involving the hepatopancreaticobiliary structures is rare. Surgical resection is examined for its role in cure or palliation. Methods: From 1997 to 2011, 151 patients were treated surgically for sarcoma involving the retroperitoneum, abdomen and pelvis. Sixty-four (42%) had primary or locally advanced/metastatic sarcoma involving the pancreas and/or liver. Results: Fifty-two of 64 (81%) patients underwent en bloc pancreas and/or liver resection. 34/52 (65%) had recurrent disease. Pancreatectomy was performed in 23 (44%), hepatectomy in 17 (33%), and combined resection in 12 (23%). The average lesion size was 12.2 +/- 8.9 cm. The average number of tumors resected at once was 4.8 +/- 7.9. Intraoperative blood loss averaged 2200 +/- 2600 cc with a mean number of blood transfusions 3.0 +/- 3.3 units. There were 4 operative deaths and 18 non-lethal perioperative complications. Pathology included gastrointestinal stromal tumor in 18 (34%), leiomyosarcoma in 16 (30%), liposarcoma in 11 (21%), and various other soft tissue sarcomas in 7 (13%). Mean follow-up was 35 +/- 41 months. 33/52 patients had tumor recurrence at a mean 15 +/- 18 months (range 2-71) after surgery. Recurrence occurred in the liver (n = 11), retroperitoneum (7), abdomen (6), pancreas (3), lung (3) and other multiple sites (3). Sixteen patients remain alive: 5 with and 11 without evidence of disease. The median survival has been 27 +/- 7 months with overall survival at 5 and 10 years 36% and 19%, respectively. Conclusions: En bloc pancreas/liver resection for sarcoma is feasible, and complete resection seems to provide worthwhile palliation or long-term survival