Unplanned Excision of Soft Tissue Sarcomas of the Extremities in a Low-to-Middle-Income Country.

BACKGROUND: Outcomes of unplanned excisions of extremity soft tissue sarcomas (STSE) range from poor to even superior compared with planned excisions in developed countries. However, little is known regarding outcomes in low-to-middle-income countries. This study aimed to determine whether definitively treated STSE patients with a previous unplanned excision have poorer oncologic outcomes compared with those with planned excisions. PATIENTS AND METHODS: Using the database of a single sarcoma practice, we reviewed 148 patients with STSE managed with definitive surgery-78 with previous unplanned excisions (UE) and 70 with planned excisions (PE). RESULTS: Median follow-up was 4.4 years. UE patients had more surgeries overall and plastic reconstructions (P < 0.001). On multivariate analysis, overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were not worse among UE patients compared with PE patients. Negative predictors for LRFS were high tumor grade (P = 0.031) and an R1 surgical margin (P < 0.001). High grade (P <0.001), local recurrence (P = 0.001), and planned excisions (P = 0.009) predicted poorer DMFS, while age over 65 years (P = 0.011) and distant metastasis predicted poorer OS (P < 0.001). CONCLUSIONS: We recommend systematic re-excision for patients with unplanned excisions. Our study shows that STSE patients with UE, when subjected to re-excision with appropriate surgical margins, can achieve oncologic results similar to those for PE patients. However, there is an associated increased number of surgeries and plastic reconstruction for UE patients. This underscores the need, especially in a resource-limited setting, for education and collaborative policies to raise awareness about STSE among patients and physicians.

The Effect of a Patient Navigator on Treatment Abandonment and Follow-up for High Grade Osteosarcoma Patients in the Philippine General Hospital.

INTRODUCTION: Treatment abandonment for osteosarcoma is a significant problem in developing countries with rates as high as 70%. This study aimed to determine the effect of a patient navigator on treatment abandonment and patient follow-up of osteosarcoma patients at a tertiary referral center. MATERIALS AND METHODS: A retrospective review of osteosarcoma patients was performed investigating 2 cohorts based on the start of the patient navigator. Group 1 (Pre-Patient Navigator, n=46) were treated from January 2016 to December 2017 while Group 2 (Post-Patient Navigator, n=29) were treated from January 2018 to June 2019. The primary outcome investigated was treatment abandonment defined as missing 4 or more consecutive weeks of treatment. Semi-structured interviews were conducted to investigate the effect of the patient navigator on the cohorts. RESULTS: Treatment abandonment rates for the Pre-Patient Navigator group was significantly higher compared to those with a patient navigator (50% vs 6%, p=0.0001). Abandonment for the pre-navigator group occurred at a mean of 2.9 months (0 - 9 months, median 3 months). Fourteen of 23 patients who abandoned from Group 1 did not proceed to neoadjuvant chemotherapy while 3 patients abandoned after completing 1 cycle of neoadjuvant chemotherapy. In the patient navigator group, no patients abandoned prior to completing 3 cycles of chemotherapy. One patient abandoned after refusing a below knee amputation after 3 cycles of neoadjuvant chemotherapy and 1 patient did not complete further chemotherapy after having a hip disarticulation. Patient feedback on the patient navigator experience was favorable. CONCLUSIONS: Having a patient navigator from diagnosis throughout treatment reduced treatment abandonment rates in osteosarcoma patients and may serve as a model for other low to middle income countries.

En bloc resection of cervical adenocarcinoma with late recurrence to the iliopsoas.

This is a case of a 50-year-old woman diagnosed with recurrent cervical adenocarcinoma presenting with chronic and persistent low back pain. She underwent myomectomy for myoma uteri 8 years prior. Histopathology report revealed cervical cancer. She underwent chemotherapy, brachytherapy and external beam radiotherapy. All surveillance work-up, over the years, were negative until she was found to have a solitary recurrent lesion in the right iliopsoas muscle on CT scan. A multidisciplinary team of surgeons collaborated to perform wide excision of pelvic recurrence en bloc right internal hemipelvectomy, right hemicolectomy en bloc resection of external iliac artery and vein, external ilio-iliac artery interposition graft and external iliac vein-common femoral vein bypass. Final histopathologic results showed adenocarcinoma with endometrioid features with associated poorly differentiated high-grade carcinoma involving the iliopsoas, cecum and terminal ileum. Two months postoperatively, the patient is ambulating with minimal assistance.

The importance of surgical margins in malignant Triton tumour of the trunk and extremities.

Malignant Triton tumour (MTT) is a rare variant of malignant peripheral nerve sheath tumour with partial rhabdomyosarcomatous differentiation. To the best of our knowledge, the importance of the surgical resection margins on the outcome of patients with MTT is unknown. The present study is a retrospective review of 24 patients treated for MTT of the trunk and the extremities between 1997 and 2015 in two institutions. The association of surgical margins with overall and tumour recurrence-free survival was analysed. Furthermore, the typical morphological and immunohistochemical characteristics of the tumour were described. In patients treated with curative intent (17/24), a surgical margin exceeding 1 mm was significantly associated with better overall survival and local recurrence-free survival. The oncological outcome was however poor, with only 28% of patients surviving at 5 years. Histopathologically, necrosis was a common feature, and most tumours displayed focal positivity for S100 protein and focal or strong positivity for desmin. The present results highlight the aggressive behaviour of MTTs and underline the importance of adequate surgical treatment.

Radical change in osteosarcoma surgical plan due to COVID-19 pandemic.

A 17-year-old man with osteosarcoma of the proximal humerus was planned for possible limb salvage surgery after standard neoadjuvant chemotherapy. However, during the surgical phase of treatment, the COVID-19 or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) outbreak occurred changing the healthcare landscape due to uncertainty regarding the virus, risk of COVID-19 infection and complications, and implementation of an enhanced community quarantine restricting movement of people within cities. Instead of limb salvage surgery, the patient underwent a forequarter amputation. Exposure to the virus in a high-risk hospital setting was minimised with patient discharge after a short hospital stay and home convalescence monitored by video conferencing. Multidisciplinary sarcoma team meetings with family members and a sarcoma navigator nurse were crucial in managing expectations and deciding on appropriate treatment in the setting of a novel infectious disease causing a pandemic.

Aggressive angiomyxoma presenting as an ischiorectal fossa tumour.

This is a case of a young healthy woman who presented with left groin pain. On work-up, she was found to have a large, well-defined mass in the ischiorectal fossa with a percutaneous biopsy of only a benign mesenchymal mass. A multidisciplinary team of surgeons (ie, colorectal, orthopaedic, vascular and urological surgery) collaborated in planning and performing the extirpation of the tumour. Final histopathology identified the tumour to be an aggressive angiomyxoma, a benign tumour with a high predilection for local recurrence. The patient had an uneventful postoperative course, with maintenance of good functional status.

Conventional Primary Central Chondrosarcoma of the Pelvis: Prognostic Factors and Outcome of Surgical Treatment in 162 Patients.

BACKGROUND: Studies focusing on the oncological outcome after treatment of conventional primary central chondrosarcoma of pelvic bone are lacking. We conducted this retrospective study at 5 referral centers to gain insight in the outcome of treatment for this tumor type and to identify risk factors for impaired oncological outcome. METHODS: One hundred and sixty-two consecutive patients (118 male patients [73%]) who underwent resection of a conventional primary central chondrosarcoma of pelvic bone from 1985 to 2013 were evaluated. The median age was 51 years (range, 15 to 78 years). The median follow-up was 12.6 years (95% confidence interval [CI], 8.4 to 16.9 years). There were 30 grade-I lesions (19%), 93 grade-II lesions (57%), and 39 grade-III lesions (24%). RESULTS: Sixty-two patients (38%) experienced local recurrence: 9 grade-I lesions (30%), 31 grade-II lesions (33%), and 22 grade-III lesions (56%). Forty-eight patients (30%) developed metastases. The risk of disease-related death was 3% for grade-I tumors (1 of 30; this patient had a grade-II recurrence and died of metastases), 33% (31 of 93) for grade-II tumors, and 54% (21 of 39) for grade-III tumors. Identified risk factors for impaired disease-specific survival were tumor grade (grade II: hazard ratio [HR], 20.18; p = 0.003; and grade III: HR, 58.94; p < 0.001), resection margins (marginal: HR, 3.21; p = 0.001; and intralesional: HR, 3.56; p < 0.001), and maximal tumor size (HR, 1.08 per cm; p = 0.026). Deep infection (19% [n = 31]) was the predominant complication. CONCLUSIONS: This study offers a standard for survival rates for conventional primary central chondrosarcoma of the pelvis. The survival for grade-I tumors was excellent. Wide resection margins were associated with a significant survival advantage for higher-grade tumors. Because of the inability to reliably distinguish low-grade and high-grade tumors preoperatively, we conclude that any central pelvic chondrosarcoma should be treated with aggressive primary resection with the aim of obtaining wide resection margins. There may be aggressive biologic features in some tumors for which a surgical procedure alone may not be adequate to improve outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Osteonecrosis of the Jaw and Rebound Hypercalcemia in Young People Treated With Denosumab for Giant Cell Tumor of Bone.

Context: Denosumab, an inhibitor of receptor activator of nuclear factor κ-B ligand, is an approved treatment of giant cell tumor of bone (GCTB) in adults and "skeletally mature" adolescents. Safety concerns include oversuppression of bone remodelling, with risk of osteonecrosis of the jaw (ONJ) and atypical femur fractures during treatment in adults and rebound hypercalcemia after treatment cessation in children. To date, ONJ has never been reported in children or adolescents. Objectives: To describe serious adverse effects during and following high-dose denosumab therapy in GCTB patients. Patients: Two adolescents (14 and 15 years) and a young adult (40 years) received fixed-dose denosumab for GCTB for 1.3 to 4 years (cumulative dose, 47 to 98 mg/kg), which was stopped because of development of ONJ in one adolescent and bilateral femoral cortical stress reactions in the young adult. All three patients developed rebound hypercalcemia with acute kidney injury 5.5 to 7 months after denosumab cessation. Results: The ONJ necessitated surgical debridement. Rebound hypercalcemia (serum calcium, 3.1 to 4.3 mmol/L) was unresponsive to hyperhydration alone, requiring repeated doses of calcitonin or intravenous bisphosphonate treatment. Hypercalcemia recurred in two patients within 4 weeks, with normal serum calcium profiles thereafter. All patients were naive to chemotherapy, radiotherapy, bisphosphonates, and corticosteroids and were metastases free, confirming the causative role of denosumab in these complications. Conclusion: These suppression-release effects of high-dose denosumab on bone remodeling raise questions about safety of fixed dosing and treatment duration. In young people, weight-adjusted dosing and safety monitoring during and after antiresorptive therapy is required.

A Novel System for the Surgical Staging of Primary High-grade Osteosarcoma: The Birmingham Classification.

BACKGROUND: Chemotherapy response and surgical margins have been shown to be associated with the risk of local recurrence in patients with osteosarcoma. However, existing surgical staging systems fail to reflect the response to chemotherapy or define an appropriate safe metric distance from the tumor that will allow complete excision and closely predict the chance of disease recurrence. We therefore sought to review a group of patients with primary high-grade osteosarcoma treated with neoadjuvant chemotherapy and surgical resection and analyzed margins and chemotherapy response in terms of local recurrence. QUESTIONS/PURPOSES: (1) What predictor or combination of predictors available to the clinician can be assessed that more reliably predict the likelihood of local recurrence? (2) Can we determine a better predictor of local recurrence-free survival than the currently applied system of surgical margins? (3) Can we determine a better predictor of overall survival than the currently applied system of surgical margins? METHODS: This retrospective study included all patients with high-grade conventional osteosarcomas without metastasis at diagnosis treated at one center between 1997 and 2012 with preoperative chemotherapy followed by resection or amputation of the primary tumor who were younger than age 50 years with minimum 24-month followup for those still alive. A total of 389 participants matched the inclusion criteria. Univariate log-rank test and multivariate Cox analyses were undertaken to identify predictors of local recurrence-free survival (LRFS). The Birmingham classification was devised on the basis of two stems: the response to chemotherapy (good response = ≥ 90% necrosis; poor response = < 90% necrosis) and margins (< 2 mm or ≥ 2 mm). The 5-year overall survival rate was 67% (95% confidence interval [CI], 61%-71%) and 47 patients developed local recurrence (12%). RESULTS: Intralesional margins (hazard ratio [HR], 9.9; 95% CI, 1.2-82; p = 0.03 versus radical margin HR, 1) and a poor response to neoadjuvant chemotherapy (HR, 3.8; 95% CI, 1.7-8.4; p = 0.001 versus good response HR, 1) were independent risk factors for local recurrence (LR). The best predictor of LR, however, was a combination of margins ≤ 2 mm and a less than 90% necrosis response to chemotherapy (Birmingham 2b HR, 19.6; 95% CI, 2.6-144; p = 0.003 versus Birmingham 1a; margin >2 mm and more than 90% necrosis HR, 1). Two-stage Cox regression model and higher Harrell's C statistic demonstrate that the Birmingham classification was superior to the Musculoskeletal Tumor Society (MSTS) margin classification for predicting LR (Harrell's C statistic Birmingham classification 0.68, MSTS criteria 0.59). A difference in overall survival was seen between groups of the Birmingham classification (log-rank test p < 0.0001), whereas the MSTS margin system was not discriminatory (log-rank test p = 0.14). CONCLUSIONS: Based on these observations, we believe that a combination of the recording of surgical margins in millimeters and the response to neoadjuvant chemotherapy can more accurately predict the risk of local recurrence than the current MSTS system. A multicenter collaboration study initiated by the International Society of Limb Salvage is recommended to test the validity of the proposed classification and if these findings are confirmed, this classification system might be considered the standard practice in oncology centers treating patients with osteosarcomas and allow more effective communication of margin status for research. LEVEL OF EVIDENCE: Level IV, prognostic study.

Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone.

Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug.

Saving a Child's Elbow Joint: A Novel Reconstruction for a Tumour of the Distal Humerus.

Reconstruction after wide resection of a malignant bone tumor can be obtained using several techniques such as the use of prostheses, allograft, autograft, or combined procedure. We describe a 12-year-old girl with parosteal osteosarcoma of the distal right humerus treated by en bloc resection, intraoperative extracorporeal irradiation, and implantation. We inserted a nonvascularised fibular autograft through the middle of irradiated graft to obtain a greater stability. We have not recorded any complication associated with this technique such as nonunion, pathological fracture, infection, and bone necrosis and we obtained an excellent functional result. 10 years after surgery, the patient had no recurrence. Extracorporeal irradiation and reimplantation is a valid and inexpensive technique for the treatment of bone tumors when there is reasonable residual bone stock. With this procedure we have a precise fit being the patient's own bone. In this way we avoid all the problems related to the adaptation of the shape and size.

The dilemma of denosumab: Salvage of a femoral head giant cell tumour.

INTRODUCTION: Denosumab is a monoclonal RANKL antibody which has been shown to be highly effective in treating giant cell tumour (GCT) of bone. We report on its use as a neo-adjuvant agent to avoid morbid surgery for an adolescent. PRESENTATION OF CASE: We report a case of a15-year old female with a Campanacci 3 GCT involving the femoral head and neck. DISCUSSION: To preserve bone stock and avoid an outright hip replacement, the patient was given denosumab pre-operatively to consolidate the tumour. After receiving 6 months of treatment, a rim of cortical bone had developed to allow an extended curettage of the tumour to be performed without fear of collapse of the articular surface. CONCLUSION: This is the first reported case of the use of denosumab in GCT of the femoral head and neck. We describe our experience in the neo-adjuvant use of denosumab and offer suggestions for future use. Further studies will be needed to see if denosumab has a role in conventional GCT and whether it can lead to a lowering of local recurrence rates.

BCOR-CCNB3 (Ewing-like) sarcoma: a clinicopathologic analysis of 10 cases, in comparison with conventional Ewing sarcoma.

BCOR-CCNB3 fusion transcripts resulting from an X-chromosomal paracentric inversion were recently identified in a series of unclassifiable soft tissue and bone sarcomas with Ewing sarcoma-like morphology. The morphologic and clinical features of these sarcomas are, as yet, not well characterized. Here we describe the clinicopathologic features of 10 cases of BCOR-CCNB3 sarcoma and compare their clinical course with typical Ewing sarcoma. Nine of 10 patients were male, and all were 11 to 18 years of age. Seven tumors were located in the bone and 3 in the deep soft tissues. The histomorphologic spectrum was quite wide, with 7 tumors predominately showing small primitive cell morphology with angulated nuclei simulating so-called atypical Ewing sarcoma and 3 predominately showing spindle cell morphology. Recurrent and metastatic lesions showed increased cellularity and marked pleomorphism. Immunohistochemistry showed expression of CCNB3 (100%), bcl2 (90%), CD99 (60%), and CD117 (60%). Reverse transcription polymerase chain reaction for BCOR-CCNB3 fusion transcripts was positive in all 9 cases, which yielded sufficient extracted RNA. Five- and 10-year survival rates were 75% and 56%, respectively. BCOR-CCNB3 sarcomas located in axial skeleton and soft tissues showed a significantly shorter survival. The Ewing sarcoma overall survival was not statistically different, although there was a trend for longer survival of patients with BCOR-CCNB3 sarcomas in the extremities. In conclusion, this study provides a detailed description of the histologic spectrum, immunohistochemical features, and clinical characteristic of BCOR-CCNB3 sarcoma justifying distinction from Ewing sarcoma with its typical EWS/FUS-ETS translocations. Ideally immunohistochemistry is used in combination with reverse transcription polymerase chain reaction for definitive diagnosis.

Aneurysmal bone cysts: do simple treatments work?

BACKGROUND: Primary aneurysmal bone cysts (ABCs) are benign, expansile bone lesions commonly treated with aggressive curettage with or without adjuvants such as cryotherapy, methacrylate cement, or phenol. It has been reported that occasionally these lesions heal spontaneously or after a pathologic fracture, and we observed that some ABCs treated at our center healed after biopsy alone. Because of this, we introduced a novel biopsy technique we call "curopsy," which is a percutaneous limited curettage at the time of biopsy, obtaining the lining membrane from various quadrants of the cyst leading to consolidation (curopsy = biopsy with intention to cure). QUESTIONS/PURPOSES: We asked whether (1) a curopsy results in comparable likelihood of healing of the ABC compared with more aggressive approaches involving curettage, (2) the two approaches differ in terms of the likelihood of recurrence after treatment, and (3) the two approaches differ in terms of complications after surgery. METHODS: Between January 1, 1999 and June 30, 2012, 221 patients with a diagnosis of primary ABC were registered in our oncology database. Patients presenting with a pathologic fracture and those seeking a second opinion were excluded. One hundred ninety patients were included in the study. One hundred two (54%) were treated with curopsy and 88 (46%) were treated with curettage after a core needle biopsy. Complete followups were available for 88% (90 of 102) and 93% (80 of 88) of patients in those groups, respectively. During that period, a curopsy was performed for all patients with benign bone lesions with imaging suggestive of classic primary ABCs and for whom the core needle biopsy simply showed blood with no solid component. Curettage after a core needle biopsy was reserved for histologically confirmed primary ABCs, lesions with impending fractures, large lesions, if the ABC was thought to be a secondary disorder, and patients for whom the curopsy failed. All patients were followed up until consolidation of the lesion (mean, 9.6 weeks, range, 3-25 weeks, 95% CI, 8.32-10.9 for curopsy; mean, 11.4 weeks, range, 8-32 weeks, 95% CI, 10.6-12.3 for curettage). The median followup for all patients was 14 months (range, 6-36 months). RESULTS: Of the 102 patients who had curopsy and observation, 83 (81%) required no additional treatment and the lesion resolved. Of the 88 patients who underwent curettage (with or without adjuvant therapy) after core needle biopsy, the success rate was 90% (79 of 88). Local recurrences in both groups (curopsy or curettage) were treated successfully with additional curettage in all but one case. Curopsy in comparison to curettage provided a mean shorter healing time (9.6 versus 11.4, p = 0.01) but there was a higher local recurrence and need for additional intervention rate (18.6% versus 10.2%, p = 0.04). There were no differences in the complications between the treatment groups. CONCLUSIONS: A curopsy is a novel biopsy technique that was successful in resolving ABCs in 81% of the patients in our study. Curopsy, as a biopsy technique, for ABCs needs consideration as it potentially minimizes the number of patients needing a second procedure (a core needle biopsy being the first) as is the current practice. Furthermore, it does not disadvantage the patient or surgeon should additional intervention be needed in the form of curettage with or without adjuvants. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Is it ever safe to discharge a chondrosarcoma of pelvis? Report of a local recurrence after 10 years.

Late local recurrence is rare in conventional pelvic chondrosarcoma. Adequacy of surgical margins is an important factor of disease control and majority of local recurrences occur within 5 years of surgery. We present a case of a 43-year-old female who underwent a PII/III resection of a Grade 1 to 2 chondrosarcoma and was discharged from routine follow-up after a 10-year disease-free interval. Thirteen years after the initial excision, she re-presented with a large local recurrence requiring a hindquarter amputation. Local recurrence more than 10 years after the index operation is uncommon in pelvic chondrosarcoma. The cases mentioned in previous studies lack documentation making recommendations on the subject difficult. Routine post-operative cross-sectional imaging is essential in pelvic chondrosarcoma even when tumour-free margins are achieved as there is no adequate adjuvant therapy to deal with microscopic disease.

Hoffa's fat pad tumours: what do we know about them?

PURPOSE: We report on a group of patients with tumours in the Hoffa's fat pad (HFP), their clinical presentation, histological type and treatment, including two synovial sarcomas with their clinical follow-up, which have not been described previously in the literature. METHODS: We performed a retrospective review of our prospectively collected database of 25 cases of HFP tumours with at least six months follow-up. RESULTS: The gender, age at presentation (over and under 16 years of age), clinical features, history of trauma, treatment chosen, and complications were recorded. The mean age of the patients was 32 years (three to 47). Six patients were under 16 years old. Pain was the most common symptom, present in 92% (n = 23/25). The final diagnoses included 23 (92%) benign tumours and two (8%) malignant tumours. The most common benign tumour was pigmented villonodular synovitis (PVNS) (48% n = 12). The two malignant tumours were synovial sarcomas and both presented in patients under 16 years old. CONCLUSIONS: Hoffa's fat pad tumours are an uncommon and rarely diagnosed group of lesions that can be misinterpreted as any knee pathology. Although the majority of HFP tumours are benign, malignant tumours should be considered in the differential diagnosis for the paediatric population.

Case report: Primary squamous cell carcinoma of a tarsal bone.

We describe a rare case of primary squamous cell carcinoma of the cuneiform bone of the foot in a 57-year-old man. In the appendicular skeleton, epithelial carcinomas of bone are usually metastatic deposits, primary squamous cell carcinomas of bone being found more frequently in the skull. A review of the English literature revealed only two other reported cases of primary squamous cell carcinoma outside the skull--one in the ilium and one in the tibia. In our patient, extensive metastatic workup and monitoring during more than 2 years showed no primary focus, supporting the rare presentation of a primary squamous cell carcinoma of bone in the appendicular skeleton.