Vol 1 | Issue 1 | July – Dec 2016 | Page 45-48 | Ajay Puri
Authors: Ajay Puri .
 Surgical Oncology, Tata Memorial Hospital, Mumbai, India.
Address of Correspondence
Dr Ajay Puri,
Chief Orthopaedic Oncology,
Prof. & Head – Surgical Oncology,
Tata Memorial Hospital, Mumbai,
This article encapsulates in brief the important publications pertaining to orthopaedic oncology that were published within the last year.
Giant cell tumor:
An article by Benevenia et al looked at the outcomes in giant cell tumors (GCTs) following standard intralesional resection-curettage and adjuvant treatment using bone graft, with or without supplemental polymethylmethacrylate (PMMA).  Complications evaluated included recurrence, fracture, and joint degeneration. Of the 43 patients included in the study 21 patients were reconstructed using femoral head allograft with or without PMMA and 22 patients were reconstructed using PMMA alone. At a mean follow up of 59 months (range, 12–234 months) non oncologic complications (articular fractures and osteoarthritis) occurred less frequently in patients treated with bone graft than those treated without (10% [two of 21] versus 55% [12 of 22]). With the numbers available, there was no difference in tumor recurrence between patients treated with bone graft versus without (29% [six of 21] versus 32% [seven of 22]). They concluded that compared with PMMA alone, the use of periarticular bone graft constructs reduces postoperative complications apparently without increasing the likelihood of tumor recurrence. Gaston and colleagues have written an excellent overview on the current status of denosumab the new “wonder drug” for giant cell tumors.  Denosumab a monoclonal antibody to RANK ligand is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumors with large soft tissue extension to allow for less morbid surgery. However the role of Denosumab for conventional limb GCT of bone is yet to be defined. Questions such as whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery and the long term use and toxicity of this agent still remain unanswered. They advise that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. So that further collaborative studies involving clinical trials and rigorous data collection may help to identify the optimum use of this drug.
A study by Wilson et al looked at the prevalence and cost of unnecessary advanced imaging studies (AIS) in the evaluation of long bone cartilaginous lesions.  A total of 105 enchondromas and 19 chondrosarcomas arising in long bones were reviewed. Advanced imaging was defined as MRI, CT, bone scan, skeletal survey, or CT biopsy. Of patients diagnosed with an enchondroma, 85 % presented with AIS. The average enchondroma patient presented with one unnecessary AIS. The average unnecessary cost per enchondroma patient was $1,346.18. Orthopaedic surgeons and radiologists need to be more pragmatic while recommending radiologic imaging in these patients as unnecessary AIS are frequently performed and are a significant source of expense. Central chondrosarcoma of bone can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas.  Although en bloc resection has been the most widely used treatment, in selected patients with low-grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment. Roitman et al evaluated the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones and its comparison with the concordance in central pelvic chondrosarcomas. Of the 126 central chondrosarcomas, 41 were located in the pelvis and the remaining 85 cases were located in long bones. The study considered 39 (95%) and 40 (47%) of them, respectively in which histological information was complete regarding preoperative and postoperative tumor grading. Concordance between the preoperative biopsy and the final pathological analysis in terms of histological grade was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (83% [33 of 40] versus 36% [14 of 39]). The authors thus concluded that image-guided needle biopsy, when performed by a specialist radiologist and evaluated by an experienced bone pathologist, is a useful tool in determining the histological grade of long-bone chondrosarcomas allowing identification of true low-grade tumors. The same appears not to be true for pelvic lesions, in which histological grade established by needle biopsy should be interpreted with caution.
Chui et al set out to identify additional histologic variables of prognostic significance in high-grade osteosarcoma.  Slides of pretreatment biopsy and primary post neoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in post treatment resections were associated with poor survival, retaining significance in multivariate analyses. A prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie,lymphovascular invasion status, mitotic rate, and extent of viable tumor) was developed. This scoring system segregated patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Laitenen and colleagues evaluated the prognostic and therapeutic factors influencing the oncological outcome of parosteal osteosarcoma.  Eighty patients with a primary parosteal osteosarcoma had an overall survival of 91.8% at five years and 87.8% at ten years. Local recurrence occurred in 14 (17.5%) patients and was associated with intralesional surgery and a large volume of tumor. 80% of the local recurrences were dedifferentiated high-grade tumors. Medullary involvement by the lesion or the use of chemotherapy had no impact on survival while Local recurrence was a poor prognostic factor for survival. The authors concluded that the role of chemotherapy in the treatment of parosteal osteosarcoma is not as obvious as it is in the treatment of conventional osteosarcoma and the mainstay of treatment is wide local excision.
A paper by Albergo and others questioned the traditional “cut off” (< / > 90 %) between poor and good responders in patient’s of Ewing’s sarcoma who had chemotherapy.  Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years. The authors concluded that only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumor in the surgical specimen. This may have implications on the addition of adjuvant therapy in the post op period, both on the need to add local radiotherapy and intensify subsequent chemotherapy in the “poor” responders.
Soft Tissue Sarcomas:
Bonvalot et al evaluated the relationship between local control and overall survival (OS) in extremity soft tissue sarcomas (ESTS).  531 consecutive patients with a median follow-up period of 7 years were reviewed. The 5-year actuarial local recurrence (LR) rate and OS were 8 % and 80 %. Predictors of worse OS were grade 3, leiomyosarcoma, male gender, and age, whereas tumor size, margin status, and LR were not. In the multivariate analysis, specific subtypes (epithelioid sarcoma and myxofibrosarcoma) and margin size < 1 mm correlated with LR, whereas grade and the tissue constituting the surgical margins did not. The authors thus concluded that specific subtypes and surgical margin size < 1 mm correlated with a higher LR while neither the margin status nor LR affect OS. Thus specific subtypes (epithelioid sarcoma and myxofibrosarcoma), which demonstrated higher LR could require larger margins to offset their bad impact. Smith and colleagues from the Royal Marsden Hospital evaluated 556 patients that underwent resection of primary extremity soft-tissue sarcoma.  They concluded that the local recurrence-free survival (LRFS) did not differ significantly between histological subtypes. Distant metastasis-free survival (DMFS) and disease-specific survival (DSS) were found to differ significantly between subtypes with the worst outcomes in patients with undifferentiated pleomorphic sarcoma. However, on multivariable analysis, histological subtype was not found to be independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in 149 patients, with the lungs being the most common site of first metastasis. The site of first metastasis differed between subtypes, with extrapulmonary metastases predominant in myxoid liposarcoma. This series suggests that the patterns of metastatic disease in extremity sarcoma are not uniform and histological subtype should be considered alongside other patient and tumor factors, such as tumor grade, size and patient age, in order to facilitate tailored follow-up regimens.
Metastatic bone disease:
Kim et all investigated whether closed intramedullary (IM) nailing with percutaneous cement augmentation was better than conventional closed nailing at relieving pain and suppressing tumors in patients with metastases of the femur and humerus.  A total of 43 underwent closed IM nailing with cement augmentation for long bone metastases. A further 27 patients, who underwent conventional closed IM nailing, served as controls. The mean pain scores of patients who underwent closed nailing with cement augmentation were significantly lower than those of the control patients post-operatively and the progression of the metastasis was suppressed in more patients who underwent closed nailing with augmentation compared to those in the control group. Thus percutaneous cement augmentation of closed IM nailing can improve the relief of pain and limit the progression of the tumor in patients with metastases to the long bones.
An article from Japan compared the infection rates after reconstructing frozen autograft with non-coated implants and iodine-coated implants (group I).  Sixty-two patients were included in group N and there were 38 patients in group I. Among other complications deep infection occurred in 10 (16.1%) patients in group N and only in one (2.6%) in group I. The authors thus concluded that using iodine-coated implants for patients with malignant bone tumor minimized risk of infection. The importance of this article lies in the fact that this novel coating may have important implications extendible to joint replacements and implants used in trauma as well. Surgical resection of desmoid tumors has traditionally been the mainstay of therapy, but this is a potentially morbid approach with high rates of recurrence. These tumors remain a management dilemma and the current trend has been towards conservative treatment rather than intervention. A retrospective analysis by Park et al identified 47 patients with a diagnosis of desmoid tumor from all anatomic sites.  20 patients were managed with surveillance, 24 patients with surgery, and three patients with other approaches. Clinical and tumor characteristics between treatment groups were not significantly different. With a median follow-up of 36 months, there was one complete regression, five partial regressions, and 13 stable diseases among the surveillance group. Only one patient under observation progressed, crossing over to surgical resection. Among 24 patients managed with surgery, 13 patients developed local recurrence. There was a statistically superior progression-free survival in the surveillance group. This data further supports the currently held belief that an initial conservative approach to desmoid tumors that may spare patients the morbidity and risk of recurrence that accompanies potentially extensive operations.
1. Benevenia J, Rivero SM, Moore J, Ippolito JA, Siegerman DA, Beebe KS, Patterson FR. Supplemental Bone Grafting in Giant Cell Tumor of the Extremity Reduces Nononcologic Complications. Clin Orthop Relat Res. 2016 Mar 1. [Epub ahead of print]
2. Gaston CL, Grimer RJ, Parry M, Stacchiotti S, Dei Tos AP, Gelderblom H, Ferrari S, Baldi GG, Jones RL, Chawla S, Casali P, LeCesne A, Blay JY, Dijkstra SP, Thomas DM, Rutkowski P . Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone. Clin Sarcoma Res. 2016 Sep 14;6(1):15.
3. Wilson RJ, Zumsteg JW, Hartley KA, Long JH, Mesko NW, Halpern JL, Schwartz HS, Holt GE. Overutilization and Cost of Advanced Imaging for Long-Bone Cartilaginous Lesions. Ann Surg Oncol. 2015 Oct;22(11):3466-73.
4. Roitman PD, Farfalli GL, Ayerza MA, Múscolo DL, Milano FE, Aponte-Tinao LA. Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones? Clin Orthop Relat Res. 2016 Feb 16. [Epub ahead of print]
5. Chui MH, Kandel RA, Wong M, Griffin AM, Bell RS, Blackstein ME, Wunder JS, Dickson BC. Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma. Arch Pathol Lab Med. 2016 Aug 23. [Epub ahead of print]
6. Laitinen M, Parry M, Albergo JI, Jeys L, Abudu A, Carter S, Sumathi V, Grimer R. The prognostic and therapeutic factors which influence the oncological outcome of parosteal osteosarcoma. Bone Joint J. 2015 Dec;97-B(12):1698-703.
7. Albergo JI, Gaston CL, Laitinen M, Darbyshire A, Jeys LM, Sumathi V, Parry M, Peake D, Carter SR, Tillman R, Abudu AT, Grimer RJ. Ewing’s sarcoma: only patients with 100% of necrosis after chemotherapy should be classified as having a good response. Bone Joint J. 2016 Aug;98-B(8):1138-44.
8. Bonvalot S, Levy A, Terrier P, Tzanis D, Bellefqih S, Le Cesne A, Le Péchoux C. Primary Extremity Soft Tissue Sarcomas: Does Local Control Impact Survival? Ann Surg Oncol. 2016 Aug 4. [Epub ahead of print] [Epub ahead of print]
9. Smith HG, Memos N, Thomas JM, Smith MJ, Strauss DC, Hayes AJ. Patterns of disease relapse in primary extremity soft-tissue sarcoma. Br J Surg. 2016 Oct;103(11):1487-96
10. Kim YI, Kang HG, Kim JH, Kim SK, Lin PP, Kim HS . Closed intramedullary nailing with percutaneous cement augmentation for long bone metastases. Bone Joint J. 2016 May;98-B(5):703-9.
11. Shirai T, Tsuchiya H, Terauchi R, Tsuchida S, Mizoshiri N, Igarashi K, Miwa S, Takeuchi A, Kimura H, Hayashi K, Yamamoto N, Kubo T. The outcomes of reconstruction using frozen autograft combined with iodine-coated implants for malignant bone tumors: compared with non-coated implants. Jpn J Clin Oncol. 2016 Aug;46(8):735-40.
12. Park JS, Nakache YP, Katz J, Boutin RD, Steffner RJ, Monjazeb AM, Canter RJ. Conservative management of desmoid tumors is safe and effective. J Surg Res. 2016 Sep;205(1):115-20.
|How to Cite this article: Puri A. Orthopaedic Oncology- Relevant articles in 2016. Journal of Clinical Orthopaedics July – Dec 2016; 1(1):45-48.