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Journal of Bone and Soft Tissue Tumors (JBST) is the official Journal of The Indian Musculo Skeletal Oncology Society


Paediatric Bone Tumours
Vol 1 | Issue 2 | Sep- Dec 2015 | page:3 | Dr Subin Sugath.
Author: Dr Subin Sugath [1].
[1]Orthopaedic Oncology Clinic, Pune, India.
[2] Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India
Address of Correspondence
Dr. Subin Sugath MS Orth.
Department of Ortho Oncology.
Aster DM Healthcare Pvt Ltd. Kuttisahib Road, Near Kothad
Bridge, South Chittoor PO, Cheranallor, Kochi 682 027,
Kerala, India.
Email: drsubin.sugath@dmhealthcare.com
Paediatric Bone Tumours
Bone tumours are rare as they constitute less than 2% of all malignancies. Though they can affect any age group, paediatric age group forms one of the commonest subsets affected by this. Osteosarcoma and Ewings Sarcoma, two common primary malignant bone tumours are commonly seen in patients less than 20 years of age. Since Ewings sarcoma was discussed in details in the last issue of the journal, the present symposium tries to cover certain general aspects of paediatric bone tumors in some details rather than discussing individual tumors. The outcome of treatment of this malignancy has seen a drastic improvement with the use of more potent chemotherapeutic drugs, newer imaging modalities which tell you the exact extent of these tumours and improved surgical techniques. The overall survival and disease free survival have increased from the dismal levels prevalent in the eighties to promising new levels. Amputation which was the choice of treatment earlier has been replaced by limb preserving surgeries where only the diseased bone is removed rather than the entire affected limb. An adult and a paediatric patient cannot be equated when it comes to management of bone tumours. The challenges in treating a child with bone tumour are more considering the age, size of the patient and bone, the remaining growth potential and the difficulty in using conventional reconstruction options after tumour resection. An open physis can be considered as a thick barrier to tumour spread and can be taken as a margin while doing tumour resection in children. The concept of margin and their implications in tumour surgery in children has been discussed in the article by Prof. K.C Gopalakrishnan [1]. The article is written from a surgical anatomy/pathology point of view and will be very helpful in understanding the basic of natural barriers and spread of tumors. Conventional reconstruction technique using prosthesis causes limb length discrepancy at the time of skeletal maturity as the unoperated limb grows normally while the operated limb doesn’t as the growth plate is also removed during the tumour excision. Different reconstruction options which can overcome this are discussed in detail in the article by Prof. Robert Grimer [2]. The decision making between limb sacrifice and limb salvage is difficult one both for the patient and for the surgeon. Factors like life span, limb function, patient’s wishes and expected limb function will help guiding the decision. At times, this decision may be quite difficult and may challenge even a lifetime experience of an orthopaedic oncology surgeon [2]. Expandable implants which can be lengthened over a period of time to compensate for the growth of the contralateral limb has come a long way in making prosthetic replacement an acceptable option in children with bone tumours. Various biological methods of reconstruction using autografts and allografts have their own advantages as it can be a lifelong solution once they incorporate with the host bone. Reimplantation of the tumour bone after sterilisation is also now accepted as a reconstruction option in children. Intercalary resections where the natural joints can be preserved require precise surgical resections to attain both oncological clearance and also to have a viable reconstruction option. Computer Assisted Orthopaedic Surgery (CAOS) has come a long way in helping to attain this goal. The benefits of this technique are explained in the article by Prof. Lee Jeys where he also discusses the use of CAOS in complex pelvic surgeries [3]. The benefits of using high dose methotrexate has been debated for long. Although methotrexate is been use since 1960’s, the currently literature still does not have enough evidence to recommend for or against its use. Some studies have shown strong positive effect while others have shown no advantage. The use of high dose methotrexate based chemotherapy has been outlined in the article by Dr Vivek Radhakrishnan [4]. They have also tried to review the important existing literature and provide recommendation for use of high dose methotrexate in paediatric osteosarcomas. Applicability of high dose methotrexate is also discussed in the Indian scenario and this may be applicable to most developing world countries. In all keeping up with the multidisciplinary approach discussed in the editorial [5], the current symposium has tried to present anatomical/pathological, surgical and medical aspect of bone tumors along with recent advances in the field. Children with bone tumours need to be treated differently from adults while considering the management and I hope these series of articles will help to enlighten us in the management of these complex problems.
Dr Subin Sugath
References
1. K C Gopalakrishnan. Natural “Barriers” Its Relevance To The Spread Of Bone Sarcoma. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):5-9.
2. Parry M, Grimer R. Limb Salvage in Paediatric Bone Tumours. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(2):10-16.
3. Archer JE, May PL, Jeys LM. CAOS in Paediatric Bone Tumour Surgery. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):17-21.
4. Reghu K S, Radhakrishnan V S. High dose Methotrexate in Paediatric Osteosarcoma – a brief overview. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):22-24.
5. Panchwagh Y, Shyam AK. M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must ! Journal of Bone and Soft Tissue Tumors Sept- Dec 2015; 1(2):1-2.
Dr.Subin Sugath
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M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must !
Journal of Bone and Soft Tissue Tumors
Vol 1 | Issue 2 | Sep- Dec 2015 | page:1-2 | Dr. Yogesh Panchwagh & Dr. Ashok Shyam.
Author: Dr. Yogesh Panchwagh [1], Dr. Ashok Shyam [2,3].
[1]Orthopaedic Oncology Clinic, Pune, India.
[2] Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India
Address of Correspondence
Dr. Yogesh Panchwagh.
Orthopaedic Oncology Clinic, 101, Vasanth plot 29, Bharat Kunj Society -2, Erandwana, Pune – 38, India.
Email: drpanchwagh@gmail.com
Editorial: M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must !
“Coming together is beginning, keeping together is progress, working together is success”: Henry Ford.
Henry Fords quote can be aptly extrapolated to the clinicians working in the field of orthopaedic oncology. Many a time, it is seen that interaction between various specialties is of paramount importance to reach to a logical conclusion while dealing with bone and soft tissue tumors. The rarity of these lesions and often-encountered complex clinical scenarios makes it mandatory for the treating clinicians to sit together to decide the diagnosis and further line of management. The multi disciplinary team (M.D.T.) that thus ensues is the key to success in management of bone and soft tissue tumors.
A typical M.D.T. comprises of (but may not be limited to) the sarcoma surgeons, medical and radiation oncologists, Pathologists, radiologists, Palliative care and rehabilitation specialists. It is expected that the institute where the M.D.T. is located should have reasonable experience in managing sarcoma patients. This number may vary from country to country. For example, In the U.K., it is expected that such an M.D.T. should be seeing at least 100 new soft tissue sarcoma cases every year or 25 primary bone sarcoma cases every year [1,3].
It is expected that all cases or suspected cases of sarcomas should have a speedy access to diagnosis and treatment. All diagnosed cases also need to be reviewed by a specialist in the M.D.T. The surgical management including the initial biopsy and definitive resection, chemotherapy and radiotherapy are to be carried out by member of a sarcoma MDT. In case that a surgeon who is a M.D.T. member is not available, the surgery should be done by a surgeon with tumor site-specific or age-appropriate skills, in consultation with the sarcoma MDT. Informing patients about relevant clinical trials and support to enroll into the trials as appropriate also forms a responsibility of the M.D.T [1,2,3,4].
Such MDT’s should be developed at individual centers that specialize in management of sarcomas. The advantages of such MDT approach is manifold. First it will allow complete and detailed assessment of patient and the disease at single center which will help in early and accurate diagnosis of the disease and extent of the disease. It will also help in more precise planning of management strategies and much better patient care. Sarcomas are unique diseases in the sense that they invoke a great sense of anxiety in the patients and their caregivers. These diseases have strong emotional responses and many a times lot of confusion exists in minds of the affected. In our country this leads to a varied response which many a times includes patient being referred and consulted by many doctors and surgeons before reaching a proper channel of care. A single coordinated MDT will help the patients to reach this channel much earlier. A coordinated approach at single center will help curb the patient’s and caregivers anxieties to a large extent and will also be much more convenient to them. The Australian Sarcoma Study Group have gone through the literature and produced evidence supporting MDT approach through following conclusions [1,2,3] :
1. MDT: Treatment at a dedicated MDT center results in better patient survival, decreased amputation risk, better chances of disease free survival. Also MDT center follow the clinical practice guidelines and have appropriate use of preoperative imaging and biopsy.
2. Supportive care: This is one of the most important aspect of patient care that help in providing better care for the patient as a whole. It helps in improving the quality of life, patients stay fewer days in the hospital, require fewer home visits and have better physical, social and emotional responses.
3. In MDT scenario the expert panel of radiologist will be able to diagnose the disease early and also pathological diagnosis is much more accurate in MDT settings.
There have been some attempt to bring together various specialties in our country too. Specifically there have been common forum and meetings where specialties have come together to share their views. Few centers have regular interspeciality meetings too. The Indian Musculoskeletal Oncology Society has organized a multifaculty meeting in Pune in October 2015 and hopefully they will continue to foster this development. Centers that specialize in sarcoma care should realize the importance of MDT approach. Although specialized centers do have coordinated approach, a more formal MDT body will help make the system more organized and effective. Journal of Bone and Soft Tissue supports the multidisciplinary approach and the first issue had authors from almost all specialist involve in sarcoma care. We wish to involve more specialties and specialist involved in sarcoma care with JBST and in coming issues our focus will be to publish articles with more coordinated approach to oncology care.
The MDT approach has been successfully used in many countries. In fact the U.S. National Cancer Control Network (NCCN) (www.nccn.org) and the U.K.s National Institute for Health and Clinical Excellence (NICE) (www.nice.org.uk) both have detailed recommendation for use of MDT approach in management of sarcomas. The developing countries too need to follow a similar model in the interests of the sarcoma patients. It is still not very uncommon in a country like India, which dreams of a digital revolution, to see examples of late diagnosis, improper biopsies, incorrect interventions and non-evidence based management. We believe that there is a need to prepare our own guidelines, modified according to suit the geography, disease prevalence and health care and infrastructural capabilities and to promote the concept of MDT in the care of sarcomas.
Yogesh Panchwagh & Ashok Shyam
References
1. National Institute for Health and Clinical Excellence, 2006. Improving outcomes for people with sarcoma. NICE guidance on cancer services.
2. Robert Grimer Nick Athanasou, Craig Gerrand, Ian Judson, Ian Lewis, Bruce Morland, David Peake, Beatrice Seddon, and Jeremy Whelan. UK Guidelines for the Management of Bone Sarcomas. Sarcoma. 2010; 2010: 317462.
3. Why Multi disciplinary care is important in sarcomas. www.australiansarcomagroup.org/multi-disciplinary-care.html
4. The ESMO / European Sarcoma Network Working Group. Bone Sarcomas: ESMO Clinical Practice Guidelines. Ann Oncol (2014) 25 (suppl 3): iii113-iii123.
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Non-Vascularised Ipsilateral Fibular strut – A Modality to Treat Giant cell tumor of lower end radius using Anterior Approach.
Vol 1 | Issue 1 | May – August 2015 | page:45-47 | Ninad Godghate[1], Vikram V Kadu[1], K A Saindane[1], Neha N Godghate[1].
Author: Ninad Godghate[1], Vikram V Kadu[1], K A Saindane[1], Neha N Godghate[1].
[1]ACPM Medical College, Dhule – 424001, Maharashtra, India
Address of Correspondence
Dr. Vikram V. Kadu
ACPM Medical College, Dhule – 424001, Maharashtra India
Email : vikram1065@gmail.com
Abstract
Introduction: Giant cell tumor is a benign bone tumor, locally aggressive with low malignant potential. The goal of treatment of this tumor at the distal radius is complete removal of the tumor and reconstruction of the bone defect in order to preserve maximum function of the wrist joint.
Case Series: This is a retrospective study conducted in 5 consecutive patients of GCT of distal radius. All patients presented with pain and swelling over distal end radius and were assessed clinically and radiographically. X-ray showed lytic lesion at lower end of radius suggestive of GCT. Histopathological examination and FNAC was done to confirm the diagnosis. Once the patient was fit for Surgery, wide excision of tumor and reconstruction with ipsilateral non-vascularised proximal fibula was performed. DCP plating was done to secure the fibular graft to the radius. 2 K – wires, 1 transverse through the fibula and ulna and 1 through fibula into the carpals were used for additional fixation and to help maintain the fibula and ulna in close approximation.
Results: At final follow up of minimum 1 year, all cases had good graft union with no recurrence. The range of motion of the wrist was near normal with no instability and good grip strength. Although this is an early follow up no graft collapse and no arthritic changes were noted. There were no complications both at donor and recipient graft sites.
Conclusion: Autogenous non-vascularised fibular graft for reconstruction of distal radius GCTcan be considered as a reasonable option for treating such conditions. Long term follow up will be needed to assess temporal complications and long term survival of the graft.
Keywords: Distal radius, fibula, GCT, ipsilateral.
Introduction
Juxta-articular giant cell tumors of the lower end radius are common and present a special problem of reconstruction after tumor excision. Various reconstructive procedures described, non-vascularised fibular autograft has been widely used with satisfactory functional results. Giant cell tumors (GCT) of the bone are aggressive and are recognised for variable clinical behaviour, which is not always related to radiographic or histological appearance [1]. Complete excision of the tumor offers the best chance of cure but sacrifices the articular surface and presents complex reconstructive problems. Giant cell tumor (GCT) of bone is a benign but locally aggressive tumor with tendency for local recurrence [2]. Distal radius is the third most commonly involved site of skeletal GCTs (10% cases) next to distal femur and proximal tibia [3,4]. Goals of treatment are to achieve satisfactory removal of the tumor, lessen the chance of local recurrence and to preserve as much wrist function as possible.
Case Series
This is a retrospective study conducted between 2004-2014. We studied 5 consecutive cases of GCT involving the distal radius operated by en-bloc resection of tumor followed by reconstruction with ipsilateral non-vascularized fibular graft with a minimum 1 year follow-up. Informed consent from the patient was taken and approval from the institutional review board was obtained for the study. Of the 5 cases studied, 3 were males and 2 were females. 3 right sided and 2 left sided. Mean age group was 22 yrs (14 – 30 yrs). Campanacci’s staging system for giant cell tumour of the bone [5] was used for cortical breach. According to this system, 2 tumours were classified as Stage I and 3 tumours as Stage II. Once the patient was medically fit, surgery (ORIF with resection of distal end of radius and reconstruction with ipsilateral non vascularised proximal fibula along with plate and 2 k-wires) was performed.
Surgical Technique
Patient supine on the operating table, with the arm on an arm board. Tourniquet on the arm was applied without exsanguinating the limb. Incision taken from the distal flexor crease of the wrist proximally upwards. The plane between the brachioradialis and flexor carpi radialis longus was used to reach upto the bone. The distal end of the radius was resected and measured. According to the measurement, the ipsilateral proximal fibula was resected and was reconstructed after giving thorough wash to the reconstruction site. The fibula was then fixed to the radius with a 6 hole DCP plate and 2 transverse k-wires at the distal end to stabilize the distal DRUJ. The path of common peroneal nerve was encased in soft tissue which was attached to proximal tibia. Closure was done and drain was kept. Below elbow slab was provided post-operatively.
Case Study
28 yrs old male presented to our OPD with complaints of pain and swelling over distal radius, moreover on the lateral side since 3 months. The swelling was initially small (Pea shaped) and gradually increased. On clinical examination, skin over the swelling was normal, swelling was diffuse and was fixed to the bone. The movements at the wrist joint was painless but the patient had tenderness on deep palpation. The egg shell crackling sign was absent on palpation. X-ray (Fig 1a) showed lytic lesion at the distal end of the radius. It was characteristic of soap bubble appearance. FNAC was done which revealed GCT. Further histopathology (Fig 1b) was done which confirmed GCT. Once the patient was medically fit, surgery (ORIF with resection of distal end of radius (Fig 1c) and reconstruction with ipsilateral non-vascularised proximal fibula along with plate and 2 k-wires) was performed. 6 hole DCP plate was used for reconstruction of the fibula to radius and 2 k-wires for additional stability to distal radio-ulnar joint. The patient was given below elbow slab post-operatively for 4 weeks and then below elbow cast for another 2 months. The arm was protected in corset for 1 yr. The 2 k-wires were removed at 3 months follow-up (Fig 1d). At 5 months follow-up (Fig 1e), patient was clinically and radiologically assessed and physiotherapy was started. At 1 yr follow-up (Fig 1f), The patient had gained acceptable range of movement with excellent grip strength, without any complication and returned to his previous work. All patients completed one year follow up and were called for final assessment. Bone graft had united in all cases with acceptable range of motion when compared to opposite side. There were no obvious complications, arthritis or recurrence.
Discussion
Giant cell tumor is an aggressive lesion with a high rate of recurrence [6]. There are reports that giant cell tumors in the lower end of the radius are more aggressive and metastasize more often to the lungs(1). Non-vascularised fibular autograft was first used in 1945 for congenital absence of radius(7). Later, fibular transplants were used by various authors for tumours of the lower end radius(8). This reconstruction technique has yielded good functional results for giant cell tumour of the lower end of the radius in various series, although large series with longer follow-ups are few(9).
In our study, we treated 5 patients with giant cell tumour of the distal radius by resection and ipsilateral non-vascularised fibular graft. Non-vascularised proximal fibular graft is reasonably congruous with distal radius and incorporated more rapidly. The graft is easily accessible without donor site morbidity. No allograft was used in our study. The patients we studied belonged to young generation in which limb salvage along with functional range of motion is the demand. The aim of treatment is to remove the tumor, reduce the chances of recurrence and preserve the joint function.
Resection of distal radius and reconstruction with ipsilateral non-vascularized fibula offers several advantages like more congruency of carpal joint, rapid incorporation as autograft and easy accessibility without significant donor site morbidity. Structural change is also minimal. Moreover, immunogenic reactions are absent. Case reports of joint preservation using vascularized fibula or prosthesis are found to be few and inconclusive(10,11]. Vascularised fibula has advantages of speeding up the healing time and early mobilization but at the same time its disadvantages includes; prolonged surgery time, need to sacrifice the arteries, skilled surgeon, not possible by an average orthopaedic surgeon.
The most commonly encountered complication in such cases are non-union, delayed union, wrist joint subluxation, subluxation of DRUJ. In our study we didn’t encounter any of the complications. Moreover, reconstruction with ipsilateral non-vascularised fibular graft is less time consuming, comparatively easy, can be done by any average orthopaedic surgeon and does not require any microvascular surgery. A proper length of fibular graft is a must to maintain the radial height and to prevent subluxation of the wrist joint. We ensured this by harvesting the fibula 2-3 mm more than the required length, which is the resected tumor length plus the safe margin. This 2-3 mm allowed us to achieve compression at the host-graft junction during fixation with DCP. A longer fibular graft will lead to subluxation of the wrist whereas 2 k-wires fixed in the distal fibula-ulnar joint further helps in stabilization of the wrist joint. There is a chance of stiffness of the wrist with relatively longer duration of immobilization and consequently decrease in the hand grip strength.
GCT of the distal radius is best treated with excision of the distal radius and reconstruction by non-vascularized fibula with good functional results[12].Our method of resection and reconstruction with non-vascularized fibular graft, internal fixation with DCP with primary bone grafting, use of stabilizing K-wires across the newly formed wrist joint and ligament reconstruction has been advocated by many other authors[13,14,15].
Clinical Message
ORIF with resection of distal end of radius and reconstruction with ipsilateral non-vascularised proximal fibula along with plate and 2 k-wires is a novel method for treating giant cell tumors of distal end of radius with all good results, excellent grip strength and with minimal complications. It also preserves the functional movement and stability with normal appearance of the wrist. Further, this procedure eliminates the need for microvascular surgery. Moreover, the anterior approach used in our study offers excellent and safe exposure of the radius.
Editor’s Note
The surgical treatment of a giant cell tumor located in the distal radius is dictated mainly by the Campanacci grading. It is accepted that the distal radius is one site where giant cell tumors have a very high rate of local recurrence. It is mainly because of the anatomical constraints and difficulty in achieving a complete intra lesional clearance. However, whenever possible, salvaging the wrist by intra lesional curettage and reconstruction has always shown much better functional outcomes as compared by the M.S.T.S. scoring system. This is possible when the disease is not involving the radio-carpal joint, the soft tissue extension is in only one plain and the residual bone stock is adequate. Campanacci grade 1 and 2 lesions and some grade 3 lesions may still be amenable to intra lesional curettage, though with a higher risk of local recurrence. This is compensated by the much better functional outcomes as compared with en bloc resections. The success of fibular reconstruction modality with wrist salvage would largely depend on regaining the wrist ligamentous and capsular stability, failure of which will result in stiff, painful wrist and carpal subluxation. Such a reconstructive modality may not be the preferred choice in very large Campanacci grade 3 lesions, wherein wrist arthrodesis either by bone graft or ulnar translocation technique gives excellent functional outcome with minimum risk of local recurrence.
References
1. Szendroi M. Giant cell tumor of bone. J Bone Joint Surg Br 2004;86:5-12.
2. Eckardt JJ, Grogan TJ. Giant cell tumour of bone. Clin Orthop. 1986;204:45–58.
3. Dahlin DC, Cupps RE, Johnson EW., Jr Giant cell tumour: A study of 195 cases. Cancer. 1970;25:1061–70.
4. Goldenberg RR, Campbell CJ, Bonfiglio M. Giant cell tumour of bone. An analysis two hundred and eighty cases. J Bone Joint Surg Am. 1970;52:619–64.
5. Campanacci M. Giant cell tumor and chondrosarcoma: grading, treatment and results. Cancer Res 1976;54:257-61.
6. Smith RJ, Mankin HJ. Allograft replacement of distal radius for giant cell tumor. J Hand Surg Am 1977;2:299-308.
7. Starr DE. Congenital absence of radius; method of surgical correction. J Bone Joint Surg 1945;27:572.
8. Parrish FF. Treatment of bone tumors by total excision and replacement with massive autologous and homologous grafts. J Bone Joint Surg Am 1966;48:968-90.
9. Murray JA, Schlafly B. Giant cell tumors in the distal end of the radius. Treatment by resection and fi bular autograft interpositional arthroplasties. J Bone Joint Surg Am 1986;68:687-94.
10. Pho RW. Malignant giant cell tumour of distal end of the radius treated by a free vascularized fibular transplant.J Bone Joint Surg Am. 1981;63:877–84.
11. Ihara K, Doi K, Sakai K, Yamamoto M, Kanchiku T, Kawai S. Vascularized fibular graft after excision of giant cell tumour of the distal radius.a case report. J Surg Oncol. 1998;68:100–3.
12. Goni V, Gill SS, Dhillon MS, Nagi ON. Reconstruction of massive skeletal defects after tumour resection. Ind J Orthop. 1992;26:13–6.
13. Deb HK, Das NK. Resection and reconstructive surgery in giant cell tumour of bone. Ind J Orthop.1992;26:13–6.
14. Dhamni IK, Jain AK, Maheswari AV, Singh MP. Giant cell tumours of the lower end of radius:problems and solutions. Ind J Orthop. 2005;39:201–5.
15. Saraf SK, Goel SC. Complications of resection and reconstruction in giant cell tumour of distal end of radius- An analysis. Ind J Orthop. 2005;39:206–11..
Dr. Ninad Godghate
Dr. Vikram V. Kadu
Dr. K. A. Saindane
Dr. Neha N Godghate
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Ewing Sarcoma: What’s in a name?
Vol 1 | Issue 1 | May – August 2015 | page:6-7 | Ashok K Shyam[1,2*]
Author: Ashok K Shyam[1,2*].
[1]Department of Orthopaedics, Sancheti Institute for Orthopaedics and Rehabilitation, Pune India.
[2]Indian Orthopaedic Research Group, Thane, India.
Address of Correspondence
Dr. Ashok K Shyam MS Orth.
Department of Orthopaedics, Sancheti Institute for Orthopaedicsand Rehabilitation, Pune India.
Email: drashokshyam@yahoo.co.uk
Abstract
There appears to be some ambiguity surrounding interpretation of collaborating disciplines on how ‘Ewing sarcoma’ is named, written or spoken. And they mostly are pretty sure about their version (or probably unaware of any other version!). The article will focus on the issue of how Ewing sarcoma is quoted in literature and shed some light on origin of the term. This will also serve as an introduction to our symposium on Management of Ewing Sarcoma.
Keywords: Ewing Sarcoma, Name.
History
Ewing sarcoma was first described by Dr James Ewing in 1921 in his paper read at New York Pathological society proceedings [1]. In his paper he described a 14 year old girl with a bone tumor arising from radius shaft which was diagnosed to be osteosarcoma. Although osteosarcomas were known to be radioresistent, this particular patient underwent radiotherapy and to everyone’s surprise had a ‘miraculous’ response both clinically and radiographically. The tumor did recur but biopsy done this time revealed it to be distinct form osteosarcoma. Ewing described the cells as round using the loose term ’round cell sarcoma’. To him the cells appeared similar to cells of endothelium of the blood vessels of the bone and thus he described the tumor as ‘Endothelioma of the bone’. He further described 6 such similar patients. This tumor was named as ‘Ewing sarcoma’ few years later by Ernest Codman [Ewing sarcoma is the most common differential of Codman Triangle] [2]. Although Dr James Ewing has contributed a lot to medicine his contributions in estabilishing oncology as an independent science is noted by naming him as ‘The Cancer Man’ or ‘Mr Cancer’ by his colleagues and media. He is still best known to every student of medicine by the eponym of ‘Ewing Sarcoma’.
What’s in the Name?
Ewing sarcoma has been reported to be written as ‘Ewing sarcoma’, Ewing’s Sarcoma’, ‘Ewings’ Sarcoma’ or simply ‘Ewings sarcoma’. Which is the correct version? I came across this issue rather accidently on preparing and reviewing for this particular symposium. We have three articles in the symposium [3,4,5], one on radiotherapy, one on medical management and one on surgical aspect. There was difference in how these three manuscripts spelled Ewing sarcoma. The non surgical articles insisted the name to be ‘Ewing Sarcoma’ while the surgical article insisted on ‘Ewing’s Sarcoma’. So what is the correct nomenclature? On sarcomahelp.com site I found this description “The tumor which bears his name is generally referred to as Ewing’s sarcoma when spoken and either Ewing’s sarcoma or Ewing sarcoma when written [6].” I reviewed the policies about the eponymus words and found an interesting fact about them. A cold war is been fought between US and Europe with US wishing to phase out use of eponyms and is against creating any new ones [7]. The argument is that the disease is not ‘Owned’ by a person. They called the eponymus use with an apostrophe as a possessive case of the word that indicates that the person either had the disease or owned the disease. By that example Ewing’s sarcoma indicates that Ewing had the sarcoma! They advocated a non possessive use of the eponyms like ‘Ewing sarcoma’. Following the rule the AMA Manual of Style: a guide to authors and editors recommends use of non-possessive case for writing eponyms. Even if we ask word nerds in true grammatical sense an apostrophe does indicate possessive nature of the noun to which it is attached. On the other hand the European literature holds the eponyms in high regards as historical testaments to physicians who first described the diseases and advice to write eponyms with an apostrophe as in Ewing’s sarcoma. To support this there remains arguments regarding using non possessive case in certain diseases like replacing ‘Down’s Syndrome’ with ‘Down syndrome’ which will then imply that there is an ‘Up Syndrome’! The controversy still rages and anyone interested should read these two articles published in British Medical Journal [8,9].
But what about our question about Ewing Sarcoma? Searching pubmed, I could find 1021 article with Ewing sarcoma , 2147 articles with Ewing’s Sarcoma , 17 article with Ewings sarcoma and 9 articles with Ewings’ sarcoma respectively in their titles (Fig 1 a-d). Thus most of them were divided into either possessive case or non-possessive case and possibly it depends on journal policy and geographical preference. Search of MESH (Medical Subject Heading) in pubmed identifies Ewing sarcoma as Mesh Major Subject Heading. I too would personally agree with non-possessive case [also as per AMA Style and Pubmed MESH term] in form of ‘Ewing Sarcoma’ although authors may choose other versions too. However when one of the version is used, authors should use the same version consistently throughout the manuscript. In this symposium we have used the non-possessive version in medical management and radiotherapy articles while a possessive version is used by the surgical focussed article. We hope the symposium is informative and any queries that remain in readers mind are welcomed as ‘Letter to Editor’ and will be answered by the respective authors.
References
1. Ewing J: Diffuse endothelioma of bone, Proc NY Pathol Soc 1921;21:17.
2. Timothy P. Cripe, “Ewing Sarcoma: An Eponym Window to History,” Sarcoma, vol. 2011, Article ID 457532
3. Valvi S & Kellie SJ. Ewing Sarcoma: Focus on Medical Management. Journal of Bone and Soft Tissue Tumors May-Aug 2015; 1(1):4-6
4. Irukulla MM, Joseph DM. Management of Ewing Sarcoma: Current Management and the Role of Radiation Therapy. Journal of Bone and Soft Tissue Tumors May-Aug 2015; 1(1):4-6
5. Panchwagh Y. Ewing Sarcoma: Focus on Surgical Management. Journal of Bone and Soft Tissue Tumors May-Aug 2015;1(1):4-6
6. http://sarcomahelp.org/ewings-sarcoma.html#tpm1_1
7. Jana N, Barik S, Arora N. Current use of medical eponyms–a need for global uniformity in scientific publications. BMC Med Res Methodol. 2009 Mar 9;9:18.
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Current role of FDG-PET in Bone and Soft tissue tumors
Vol 1 | Issue 1 | May – August 2015 | page:29-36 | Junaid Ansari[1], Reinhold Munker[1], Amol Takalkar[2,3*].
Author: Junaid Ansari[1], Reinhold Munker[1], Amol Takalkar[2,3*].
[1]Feist Weiller Cancer Center, Shreveport, Louisiana.
[2]Center for Molecular Imaging & Therapy, Biomedical Research Foundation of Northwest Louisiana.
[3]Dept. of Radiology, LSU Health, Shreveport, Louisiana.
Address of Correspondence
Dr. Amol Takalkar MD.
Dept. of Radiology, Louisiana State University Health Sciences Center – Shreveport, 1505 Kings Highway, Shreveport, LA 71103
Email: atakalka@biomed.org
Abstract
FDG-PET/CT imaging is an established modality for the workup of several malignancies; it is now considered standard for the initial as well as a subsequent treatment strategy in the management of most malignancies. The focus of this article is to discuss the role of FDG-PET/CT imaging in the workup and management of malignant bone and soft tissue tumors in conjunction with standard imaging techniques like MRI and CT scanning. The article also briefly touches upon the potential role of emerging PET-MRI modality.
Keywords: FDG-PET, Musculoskeletal tumors, Bone tumors, CT, MRI, Ewing Tumors, Osteosarcoma, GIST.
FDG PET and PET/CT
Positron emission tomography (PET) is a non-invasive nuclear imaging technique which relies on the detection of positrons emitted during the decay of a radionuclide and maps the biodistribution of the administered radiopharmaceutical. Compounds of interest are labelled with a positron-emitting radiotracer and infused and distributed according to the in vivo biologic behavior of the tagged compound. 18F-fluorodeoxyglucose (FDG) is the most commonly used PET radiopharmaceutical for oncology. FDG is a glucose analog in which the hydroxyl group is replaced by positron-emitting fluorine isotope (18F) and FDG-PET or FDG-PET/CT (when PET is combined with computed tomography) provides a map of glucose metabolism in the body. In contrast to anatomical and morphological approaches, FDG-PET provides more metabolic and functional information about the disease and can be an important imaging tool to non-invasively understand cancer biology [1]. FDG is actively taken up by cancer cells and remains metabolically trapped intracellularly. Otto Warburg, a German physiologist in the 1920’s, had shown that most tumor cells generate energy by non-oxidative breakdown of glucose and are hypermetabolic compared to the normal cells (The Warburg Effect). FDG-PET exploits this effect as cancer cells take up more FDG than normal cells and are hence detected on imaging as regions of increased FDG uptake. The concept of FDG-PET was developed in the 1970’s when it was used for functional brain imaging and then in the 1980’s to assess the cardiac metabolism. However, over the past 15 to 20 years, oncologic indications have become the predominant use for FDG-PET imaging and along with technological advances, it has now evolved to integrated PET/CT systems that provide highly sophisticated information with implementation of further hybrid imaging technologies, like combined PET/MRI, on the horizon [2].
With notable exceptions (such as prostate cancer), FDG PET/CT is routinely used for the initial treatment strategy (formerly encompassing diagnosis and staging) as well as a subsequent treatment strategy (formerly encompassing restaging and assessing treatment response as well as disease status) for most cancers, such as: lymphomas, lung cancer, colorectal cancer, melanomas, head and neck cancer, breast cancer, and musculoskeletal tumors and other malignancies. PET has largely been replaced by PET/CT scanners (at least in the Western nations) and this article will largely focus on PET/CT imaging instead of stand-alone PET imaging. Since MRI plays an important role in the evaluation of bone lesions, this article will briefly discuss the potential for combined PET/MRI hybrid imaging in the setting of bone and musculoskeletal tumors.
Musculoskeletal tumors
Malignant musculoskeletal tumors, also known as sarcomas, are rare and account for about 1% of cancer deaths in the United States [3]. They are a heterogeneous group of mesenchymal malignancies arising from bone and soft tissues. Primary bone tumors are seen more commonly in adolescents and younger adults, while primary soft tissue sarcomas are seen more commonly in adolescents with a second peak in the fifth decade. However, these sarcomas can affect all age groups. The World Health Organization’s classification of soft tissue sarcomas is based on the tissue of origin which continues to evolve with the discovery of new molecular genetic abnormalities [4]. The majority of soft tissue sarcomas are sporadic and only a few are linked to environmental factors like exposure to radiation, burns, toxins, viruses like HHV-8 causing Kaposi sarcoma in HIV patients, immunodeficiency syndromes, and germline mutations in Li-Fraumeni syndrome, neurofibromatosis 1, and Gardner syndrome. The common examples of soft tissue sarcomas include liposarcoma, synovial sarcoma, leiomyosarcoma (LMS), rhabdomyosarcoma (RMS), fibrosarcoma, and angiosarcoma. The patients usually present with an asymptomatic mass. The primary diagnosis is made by a tissue biopsy and imaging studies like plain radiograph, CT and MRI. Lungs are the most common site of metastases, and hence a plain radiograph and CT scan of the chest is also advisable. Treatment is based on AJCC staging. Stage IA (T1a-1b,N0,M0,G1,GX) and Stage IB (T2a-2b,N0,M0,G1,GX), low grade patients are usually managed by surgery by obtaining adequate oncologic margins. Stage IIA (T1a-b,N0,M0,G2,G3) can be managed with surgery alone, or surgery followed by radiotherapy or preoperative radiotherapy followed by surgery. Stage IIB (T2a-b,N0,M0,G2,G3) and Stage III (T2a,T2b,N0.M0,G3 and any T,N1,M0, Any G) if resectable with acceptable functional outcomes are managed with surgery followed by radiotherapy and adjuvant chemotherapy, or preoperative chemo-radiotherapy followed by surgery followed by adjuvant chemo-radiotherapy. Unresectable and resectable with adverse functional outcomes Stage II and III are managed with radiotherapy, chemotherapy, chemo-radiotherapy, or palliative surgery, alone or in combination. Synchronous Stage IV with single organ involvement or limited tumor bulk that are amenable to local therapy are managed primarily like Stage II and III tumors. Disseminated metastases are managed with palliative options. Accurate staging is critical for determining the appropriate treatment.
Gastrointestinal stromal tumors (GISTs) are discrete forms of sarcomas and are the most common abdominal mesenchymal tumors. They can arise anywhere in the gastrointestinal tract with the stomach being the most common site. Due to identification of driver mutations in the c-KIT and platelet-derived growth factor alpha genes encoding tyrosine kinase receptors, the treatment of GIST has been a role model of targeted therapy with Imatinib mesilate, a tyrosine kinase inhibitor [5, 6]. Surgery is still the main stay of management in resectable non-metastatic lesions with Imatinib playing an adjuvant role [7]. GISTs have variable clinical behavior with some presenting with nonspecific symptoms and some detected incidentally.
Bone sarcomas occur less commonly than soft tissue sarcomas and will account for 0.18% of all new malignancies, with 2970 estimated new cases and 1490 estimated deaths in the US in 2015 [3]. They are classified by Musculoskeletal Tumor Society Staging System based on grade and compartment localization. Osteosarcoma accounts for almost half of the bone sarcomas and is seen mainly in children and adolescent males in the metaphysis of long bones, especially the femur, the proximal tibia and the proximal humerus. Most of the cases are sporadic in nature with few cases arising from inherited genetic diseases like hereditary retinoblastoma and Li-Fraumeni syndrome. The patients usually present with pain and swelling of the affected area. Osteosarcomas are usually detected on imaging studies. The diagnosis is made by tissue sampling and pathology and can be suggested by imaging studies. These are usually high grade tumors with aggressive biological features and are found in or adjacent to areas with high bone growth, with subdetectable tumor spread elsewhere in majority of the cases [8, 9]. They are managed by neoadjuvant chemotherapy, which shrinks the tumor and targets micrometastatic tumor cells, followed by limb sparing surgery and adjuvant chemotherapy [9]. The prognosis is based on the response to chemotherapy. Radiation therapy generally has a limited role in the management of these tumors and is used mainly for unresectable and relapsed lesions [10]. Chondrosarcomas account for almost 25% of all bone sarcomas and are seen mainly in adult and old patients with predilection for flat bones. They have variable clinical behavior with an indolent nature and low metastatic potential [11]. Surgical resection is the standard of treatment. Radiation therapy is given in unresectable lesions. Chemotherapy is the primary therapy for systemic recurrence[10]. Ewing sarcoma constitutes approximately 10-15% of all bone sarcomas and is mainly seen in the second decade of life involving the diaphyseal region of the long bones, mostly in the lower extremity. These sarcomas present with localized pain or swelling of short duration. Constitutional symptoms are seen in small percentage of patients on presentation. They belong to a family of tumors known as PNETs (Primitive neuroectodermal tumors) and are associated with t(11;22) translocation[12]. The disease is aggressive and the presence of widespread metastasis is a sign of poor prognosis. It is primarily treated by multiagent chemotherapy and based on the response, is subsequently managed with radiotherapy, surgery or chemotherapy [10].
Improved diagnostic imaging has changed the primary management of musculoskeletal tumors. MRI is still the primary imaging technique used in detecting lesions and local staging due to its pluridirectional capabilities and superior contrast resolution. MRI thus plays an essential role in surgical planning by providing detailed information about the local extent of the disease and involvement of locoregional structures. MRIs are not, however, able to determine the subtypes of soft tissue sarcomas or differentiate between benign and malignant lesions. The regional nature of MRI also precludes identification of lymph nodes outside of the imaginary plane. Imaging distant metastatic disease is also not practical with routine MRI imaging studies. CT scans are not very sensitive for osseous pathology. Although CT has excellent spatial resolution, it is suboptimal to MRI when it comes to contrast resolution and soft tissue differentiation. CT scans are mainly used to assess pulmonary metastases and for staging of disease in the lungs in such patients [13]. Although used for assessing response to treatment based on shrinkage of the primary lesion, this approach may not be the best in the era of molecular imaging. Both CT and MRI have limitations in assessing local recurrence with altered anatomy and presence of post-therapy changes.
FDG PET/CT is not the optimal modality to assess the T-stage of these lesions. Although it can provide metabolic and functional information related to tumor biology, it has lower spatial resolution compared to morphologic imaging modalities and does not provide the intimate details about the local extent and invasiveness of the tumor. However, the intensity of FDG uptake can aid diagnosis by providing better targets for biopsy and increase the yield from biopsies. FDG PET imaging can also overcome some of the limitations of MRI, by separating high- from low-grade tumors, in determining the biological activity of a tumor, and by allowing the detection of abnormal lymph nodes and occult distant metastases, including pulmonary metastases, especially by virtue of almost whole body imaging [13]. However few studies have demonstrated that PET is less sensitive than CT scanning in the detection of pulmonary metastases and a significant number of known pulmonary metastases greater than 1.0 cm on CT, are PET negative (micro-metastases) [14]. Evolution of hybrid PET/MR may be a more efficient diagnostic modality in the future. It can provide additional information regarding soft-tissue analysis, tumor detection, tissue characterization, functional imaging and biological landscape at the same time.
Specific role of PET in musculoskeletal tumors
MRI and CT scanning are still the most commonly used imaging techniques to evaluate bone and soft tissue tumors with known limitations as discussed above. FDG-PET/CT imaging is now routine for cancer workup and the addition of a CT component in integrated PET/CT scanners have made this quite a reliable tool that can provide additional information about the biological behavior of the tumor and can aid in the management of these tumors.
Most soft and bone tumors are FDG-avid and the degree of avidity is usually associated with their clinical outcomes. In soft tissue sarcomas, FDG-PET is able to detect intermediate and high-grade lesions due to their high FDG uptake, but is not able to differentiate between benign and low-grade sarcomas since both of them tend to show low FDG uptake. Dual phase/delayed PET imaging can help in differentiating benign from malignant lesions in some cases as malignant lesions show increasing uptake on delayed images [15]. In bone tumors, low FDG uptake is usually seen in a benign lesion, with high FDG uptake in a malignant lesion. However, the highest FDG uptake is seen in metastases [16]. There are few exceptions to this rule; malignant tumors like plasmacytoma and low-grade chondrosarcoma can have low uptake, and benign tumors with either involvement of giant cells (giant cell tumor of bone) or histiocytic cells (Langerhans cells histiocytosis) can have high uptake. Using a TBR (tumor-to-background ratio) of 3.0 as a positive for malignant bone lesions, FDG PET has a specificity of 67% and a sensitivity of 93% in bone tumors [17]. The latest imaging guidelines set by Children’s Oncology Group Bone Tumor Committee highly recommend FDG-PET as a part of functional imaging in osteosarcoma and Ewing sarcomas at presentation and prior to surgery/local control. It also maintains use of FDG-PET for surveillance during and post chemotherapy [18].
Initial Treatment Strategy
Diagnosis of musculoskeletal tumors is usually established on the basis of directed biopsies after the detection of a mass on clinical exam and/or imaging. As discussed above, they are staged per the AJCC system using the TNM staging criteria. Along with clinical evaluation, contrast enhanced CT and MRI are extremely useful for optimal assessment of the “T” stage as they provide further structural information regarding tumor extension and involvement of adjacent structures. FDG-PET imaging lacks the spatial resolution to provide such exquisite structural details necessary for adequate “T” staging. However, FDG-PET can still play a role in the diagnosis of these tumors. Many of these lesions can be heterogenous and initial biopsy can be “non-diagnostic”. (Figure 1 demonstrates the value of FDG-PET in a patient with a negative/non-contributory biopsy). Since FDG PET relies on the biologic characteristics of the tumor and provides metabolic and functional information, it can be suited in such difficult cases to direct biopsies to the appropriate target site and improve the yield from biopsies. In addition, it can play an important role in the detection of locoregional metastatic lymphadenopathy and distant metastatic disease. Traditional anatomical evaluation of nodal involvement in the malignancies is sub-optimal since nodes may be enlarged as a result of infection/inflammation (that is not uncommon in the groin region), and normal sized nodes can frequently be involved with metastatic disease leading to inaccurate upstaging or downstaging of the disease with conventional imaging methods. FDG-PET (and especially PET/CT) imaging can have a tremendous impact in improving the nodal staging of sarcomas cancers compared to CT/MR (sensitivity: 87-90% versus 61-90% and specificity: 80-93% versus 21-100%) [19]. FDG-PET imaging frequently detects metastatic disease in normal-sized lymph nodes. However, caution is recommended in N0 disease per PET as micrometastases cannot be detected by FDG-PET imaging and hence the management of such patients should not solely be determined by FDG-PET findings; other techniques like surgical lymph node dissection should be employed for optimal “N” staging in such patients. Also, sometimes malignant lymph nodes with large extensive central necrosis can be falsely negative on FDG-PET with only mild FDG uptake at the periphery or no uptake at all. However, the most important added value of FDG-PET imaging is the detection of unsuspected distant metastases that can lead to dramatic changes in patient management. By virtue of its near whole body imaging and reliance on metabolic information, it has the potential to detect unsuspected occult metastases and change the management significantly. Moreover, FDG PET imaging is useful in therapy planning for patients undergoing radiation therapy with a curative or palliative intent or as neoadjuvant therapy. The increasing implementation of intensity modulated radiation therapy (IMRT) is well complemented by the additional functional/metabolic information provided by the FDG imaging, as it allows delivery of maximal radiation dose to the most metabolically active areas of the tumor and more complete inclusion of loco-regional disease with sparing of the uninvolved areas.
Subsequent Treatment Strategy
In addition to the above, FDG-PET imaging probably has an important benefit in assessing response to therapy and restaging of musculoskeletal tumors [20-23]. Following surgery or radiation therapy, it is extremely difficult to assess the treated area with conventional imaging modalities like CT/MRI due to inflammatory changes with fibrosis, edema and alteration of normal structures. Determining whether residual neoplasm is present in the postsurgical/postradiated tumor bed is one of the most daunting tasks facing radiologists. When compared to conventional radiological examination, FDG-PET has a better diagnostic accuracy in the assessment of residual or recurrent malignant disease in the post-therapeutic region, including avoidance of unnecessary planned surgery in patients with negative PET. Lack of any significant FDG uptake in the treated area generally indicates no active residual/recurrent disease. There may be some mild to modest irregular FDG uptake related to post-therapy changes, but generally there should be no gross intense focal abnormalities. Dual-phase PET imaging/delayed PET imaging may help in distinguishing post-therapeutic inflammatory changes from cancerous tissue. It may also help in the prediction of PFS (Progression free survival) and OS (overall survival). Focal intense FDG uptake within the area of post-surgical change is worrisome and needs further workup. A negative tissue biopsy after a strongly positive post-treatment PET scan can be caused by sampling error and warrants a closer follow-up rather than routine surveillance. Decrease in the intensity of uptake on the follow-up scan confirms a false positive post-treatment PET scan, usually due to inflammatory changes. However, persistence of a focally intense lesion or increase in the intensity of uptake warrants invasive evaluation. The timing of the post-treatment PET scan is very crucial, especially after radiation therapy. Although there are no specific recommendations in this regards, generally a 3-month interval after completing radiation therapy is felt to be adequate to assess response to therapy. The superior assessment of response to therapy with FDG-PET imaging may facilitate a more conservative approach in management, as patients undergoing combined chemo-radiation therapy with a complete response on the post-treatment FDG-PET scan can be followed with a more watchful approach.
There are several limitations of FDG-PET imaging in the evaluation of musculoskeletal tumors. Although it may detect tumors that may be missed by anatomic imaging (especially in-transit metastases as in Figure 2), the sub-optimal spatial resolution of PET imaging (compared to CT/MRI) limits the evaluation of local extent and invasiveness of the tumor. Also, low-grade tumors may be missed on PET if there is significant intense physiologic FDG uptake in an adjacent structure (like muscle). Conditions like joint inflammation, muscle contraction, radiation induced inflammation and osteoradionecrosis need to be kept in mind when interpreting FDG-PET studies in musculoskeletal pathology. The added information from CT images in a dedicated PET/CT scan can further help to discern this uptake as benign/physiologic.
Osteosarcoma
After the advent of neo-adjuvant chemotherapy in osteosarcoma, which has dramatically improved the prognosis, there has been a need for better imaging modality for tumor staging and grading, pre- and post-treatment evaluation, and detection of tumor recurrence (Figure 3 demonstrates FDG uptake may be quite heterogeneous and intense in osteosarcoma).
Initial Treatment Strategy
FDG-PET/CT imaging has a limited role in the initial workup of osteosarcoma. It is limited in its ability to diagnose osteosarcoma (which definitely requires tissue sampling) and is suboptimal to CT/MRI in delineating the local extent and invasiveness. The correlation between the histological grading and the FDG avidity has been well documented by several studies [24]. However, FDG-PET/CT imaging cannot obviate the need for the tumor biopsy to differentiate between a benign and a malignant lesion and establish the underlying pathology. The highest SUV values are seen in bone metastases. MRI and plain radiographs are still the first line diagnostic tools in staging the disease. In children, there may be an indication of FDG-PET in cases of unequivocal MRI findings due to physiological red blood marrow distribution to detect interosseous skip metastases. Lymph node metastasis is a rare phenomenon in osteosarcoma and hence the need of PET is limited. About 80% of metastases in osteosarcoma involve the lungs and early detection is important. The method of choice for detecting lung metastases is spiral high-resolution CT as PET can miss smaller lung lesions [25] However, whole body imaging in PET has an advantage of finding other sites of occult metastases, which cannot be seen with CT or MRI due to limited field of scanning and so should be employed in situations where clinical suspicion for metastatic disease is high. Infrequently, it may be used to guide biopsies if clinically necessary.
SUVmax and TLG (Total lesion glycolysis) are both strong prognostic factors that can predict progression-free survival, overall survival, and tumor necrosis in osteosarcoma [26].
Subsequent Treatment Strategy
FDG-PET plays a more established role in assessing therapy response and detecting recurrence. It has also been able to predict the tumor response as it relies on functional and metabolic parameters rather than structural changes. Tumor metabolic changes detected by FDG-PET precede morphological changes on anatomic imaging and early evaluation of tumor response allows treatment to be tailored to the individual. In two different studies, FDG-PET was found to be superior to MRI in the assessment of response [20, 21]. There is a direct correlation between SUV and histological grade. SUVmax reduction after therapy is the biggest indicator of whether the patient is responding to therapy or not, and based on this, the therapy can be modulated accordingly. SUVmax > 5 after neoadjuvant therapy is arbitrarily defined as a histological nonresponder and ≤ 2 as a responder [20-22, 27]. Byun et al suggested that the combination of FDG-PET/CT and MRI may be the best way to determine histological response of osteosarcoma after neoadjuvant chemotherapy [23]. The availability of combined PET/MRI imaging in the future may facilitate this.
FDG-PET has also a significant role in the assessment of tumor recurrence and restaging of high risk osteosarcoma patients. (28) It is also more accurate than other imaging studies in differentiating post-therapeutic fibrosis or inflammatory changes from local recurrence [25].
Chondrosarcomas
These sarcomas have less FDG uptake than other sarcomas owing to their high level of acellular gelatinous matrix and lower mitotic rates. Average FDG uptake of chondrosarcoma is as high as Ewing sarcoma but lower than osteosarcoma [29]. The role of PET in the diagnosis and management of chondrosarcoma is almost the same as with other malignant bone lesions. The biological activity helps to assess the tumor grade and to differentiate between benign and malignant tissue, and the whole body imaging helps to identify any occult metastases. Grade II and III chondrosarcomas have higher glucose metabolism and can be easily distinguished from a benign tumor; Grade I chondrosarcomas/atypical cartilaginous tumors cannot be so easily distinguished because of apparently similar metabolism rates [30]. (Figure 4 demonstrates the heterogeneous nature of FDG uptake in chondrosarcoma; intense FDG uptake site can help in guiding the biopsy in such patients)
Ewing sarcomas
Ewing sarcomas are high-grade malignancies and high SUVs are usually seen. PET is very sensitive in the detection of primary and recurrent lesions. PET is also superior to bone scan in detecting bone metastases and is used as a part of metastatic workup. PET has low sensitivity for smaller lesions, especially in lungs which are a common site of metastases for Ewing sarcomas and a CT scan is a superior imaging modality in such cases. PET can also be used for monitoring the tumor response to chemotherapy and radiotherapy and the possibility of a recurrence post-operatively. PET has a limitation in differentiating malignant from inflammatory lesions and cannot be used as a non-invasive diagnostic tool between Ewing sarcoma and osteomyelitis, which are frequently indistinguishable [31].
Fibrosarcoma
Fibrosarcomas arising from polyostotic fibrous dysplasia have intense FDG uptake indicating sarcomatous transformation. Fibrous dysplasia sarcomas are well known to have intense FDG uptake despite their benign nature [32]. Fibrous synovial sarcomas originate from the mesenchymal tissue and their histological appearance resembles the synovium. FDG-PET can also be used for the staging of these malignant tumors. (Figure 5 demonstrates intensely FDG avid soft tissue mass)
Gastrointestinal stromal tumors
Metabolic imaging with FDG-PET in GIST has proven to be an effective tool to evaluate the treatment response with tyrosine kinase inhibitors like imatinib. The functional imaging with FDG-PET provides earlier evidence of response in comparison to morphological changes seen with a CT scan. Jager et al observed that changes in tumor metabolism were seen as early as 1 week after the start of the treatment, which helped in delineating responders from non-responders in 14/15 cases [33]. Studies done by Stroobants et al and Goerres et al showed that PET responders had a better progression free survival and better prognosis than PET non-responders with residual FDG activity.(34, 35) However a recent study done by Chacon et al showed the early metabolic response (EMR) does not correlate with the progression-free survival or overall survival in patients with metastatic GIST. (36) GIST-specific molecular tracers are also in the making which can provide more accurate prognosis and development of treatment resistance. (37) FDG negativity however does not preclude the diagnosis of a GIST [38] (Figure 6 demonstrates the value of FDG-PET as a prognostic tool in the management of GIST)
Benign Tumors
FDG-PET has a limited role in the management of benign musculoskeletal tumors. Benign soft tissue lesions usually do not have substantial FDG uptake. Fibrous dysplasia can have variable FDG uptake, and in some cases intense FDG activity. In such situations, it is important to differentiate benign tumors from any possibility of a sarcomatous changes [39]. Hemangiomas can also be a site of intense FDG activity which can sometimes mimic metastasis. Lipomas have the lowest uptake. Careful history, physical examinations and other imaging tests like CT and MRI should help in the accurate diagnosis.
Conclusion
The evolution of PET in the recent years has changed the previous paradigm in the management of malignancies. In general, it is not the primary diagnostic modality for workup of musculoskeletal tumors but can play a role in certain clinical scenarios. Along with other imaging techniques, FDG PET/CT plays an important role in musculoskeletal tumors by guiding biopsies in heterogeneous tumors, predicting tumor response to preoperative neo-adjuvant chemotherapy, detecting skip metastases and reflecting risk of recurrence and prognosis. It also plays a more robust role in subsequent treatment strategy. Overall, it is more useful in evaluating primary soft tissue tumors relative to primary osseous lesions. However, the potential availability of integrated PET/MRI may allow for a more robust role for FDG-PET imaging in the workup of primary osseous tumors as well. FDG-avidity correlates negatively with survival and positively with disease progression. It can be used to tailor treatment, surgical versus chemo-radiotherapy. More prospective trials are needed to develop new tracers that can be more specific and lead to higher signal to noise ratio (SNR), which may help in establishing the response to treatment with newer agents and can set guidelines. Suboptimal T-stage and heterogeneous uptake in some cases, insufficient topography, radiation exposure and higher costs are a few of the limitations of using FDG-PET. In the current times, its role is still considered as an adjunct and has not replaced MRI and CT scanning. The combined PET-MRI multimodality imaging systems can provide adequate information about the morphology as well as the metabolic status of the lesion in a single imaging session and may potentially become the standard of imaging for musculoskeletal tumors in the near future. Precision medicine (prevention and treatment strategies that take individual variability into account) is the way to the future. Adopting global disease assessment, radiotherapy fractionation, imaging hypoxia, adaptive radiotherapy as part of quantifiable methodologies and standardization of FDG-PET, it can become a powerful tool for the diagnosis, individual treatment planning and subsequent treatment strategy. The absolute potential of FDG-PET in various malignancies including musculoskeletal tumors is still a work in progress and is evolving at a rapid pace with the recent development of radiopharmaceuticals and technological advancements..
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Re implantation of Sterilised tumour bone by Extra Corporeal Radiotherapy
Vol 1 | Issue 1 | May – August 2015 | page:37-39 | Subin Sugath[1*].
Author: Subin Sugath[1*].
[1]Department of Aster Orthopaedics, Aster DM Healthcare Pvt Ltd., Kochi 682 027, Kerala, India.
Address of Correspondence
Dr. Subin Sugath MS Orth.
Department of Ortho Oncology. Aster DM Healthcare Pvt Ltd. Kuttisahib Road, Near Kothad Bridge, South Chittoor PO, Cheranallor, Kochi 682 027, Kerala, India.
Email: drsubin.sugath@dmhealthcare.com
Abstract
With the use of potent chemotherapeutic drugs, newer imaging modalities and improved surgical techniques limb preserving surgeries for malignant bone tumours have become the norm. Endoprosthesis still remains the commonest method of reconstruction after tumour resection. But when one is able to an oncologically safe intercalary resection for malignant bone tumours one method of reconstruction is reimplanting the resected tumour bone after sterilisation. Radiation given outside the body to sterilise the tumour bone is called Extra Corporeal Radiotherapy (ECRT). After resection the bone is cleaned of all its soft tissue and marrow contents and sent in a plastic container to the Radiotherapy department where it is subjected to 50 Gy of radiation which kills all cells including the tumour cells. The bone is brought back to the theatre and reimplanted after augmenting it with either bone cement or fibular grafts and stabilised by appropriate fixation devices. The advantage of reimplanting the same bone is that you get an exact match to the resected bone which is tumour free. Post operatively the joint is mobilised immediately and weight bearing started as appropriate to the fixation used. The diaphyseal end takes more time to unite than the metaphyseal end. In our series of 16 patients who had undergone ECRT and reimplantation for malignant bone tumours of the extremity and had completed two year follow up, the metaphyseal end took an average of 6.2 months (4 – 12 months) for union while the diaphyseal end united in 10.6 months (5 – 15 months). If the tumour has caused extensive destruction of the bone or has a pathological fracture, it may be mechanically not sound to reimplant it after ECRT. ECRT is an oncologically safe and mechanically stable procedure in biologically reconstructing bony defects after tumour resection.
Keywords: Extra Corporeal Radiotherapy, Bone tumour, intercalary resection.
Introduction
With the use of potent chemotherapeutic drugs, newer imaging modalities and improved surgical techniques limb preserving surgeries for malignant bone tumours have become the norm. Endoprosthetic replacement is the most commonest method used to bridge the bone defect after tumour resection [1]. Such resection commonly involve resection of the growth physis across the joint leading to limb length disparity as the child grows. To overcome this, one will have to use a growing prosthesis which can be lengthened post operatively either by invasive or non invasive techniques to compensate for the growth of the normal limb [2] These implants are expensive and are not affordable to majority of patients who undergo limb salvage surgery in our country
At times, especially in young children where the open physis can be taken as a wide margin the tumour can be resected with wide margins sparing the joint ant the physis. The bone defects after these resection can be bridged by intercalary implants or size matched allografts if one has access to good tissue bank. Biological method of reconstruction has the advantage that once it incorporates with the host bone it is a life long procedure and is not associated with the complications of using a prosthesis [3,4]. Alternative technique of biological reconstruction if one does not have access to a tissue bank would be to use a vacularised or non vascularised autograft like fibula. But at times it would be impossible to harvest enough autografts to bridge large bony defects [5]. Sterilising and reimplanting the resected tumour bone is a viable option in these situations.
The advantage of reimplanting the same bone is that you get an exact match to the resected bone which is tumour free. The different methods used to sterilise tumour bone are autoclaving, pasteurisation, liquid nitrogen and radiotherapy [6]. Autoclaving involves sterilising the bone at 1210 C for 20 minutes which kills all tumour cells. But it has got the disadvantage that it reduces the bone strength as well as destroys the Bone Morphogenic Protein (BMP) [7]. Sterilising the specimen in a water bath at 650 C for 30 minutes is called pasteurisation. It has the advantage it retains the bone strength and BMP but has the practical difficulty of maintain the sterility during the procedure [6,8]. The most common method of sterilisation technique used is radiotherapy. 50 Gy of single shot high dose radiotherapy is used to sterilise the tumor bone. The procedure of giving radiotherapy outside the human body is called Extra Corporeal Radiotherapy (ECRT). The dose of radiotherapy given is so high that it destroys all cells including the tumour cells which necessitates this dose to be given outside the human body. The mechanical strength of the bone is least affected by this procedure and there are enough publications in literature which show this to be an oncological safe procedure in sterilising tumour bone. 50 Gy of radiotherapy is sufficient in attain tumour kill [9,10,11] and any higher dose of radiation decreases the mechanical strength and revascularisation and delays graft union and incorporation. The resection is made as per the pre operative imagings (Fig 1a). Marrow curettings from both the proximal and distal cut ends are send for frozen study to ensure adequacy of tumour clearance. Intercalary resected specimen with soft tissue cover over the tumour. Now the bone is completely stripped of all its soft tissue, periosteum and medullary contents (Fig 1b). The soft tissue removed is oriented with suture tags so that adequacy of tumour clearance can be assessed by histopathological examination. The bone is thoroughly washed with Vacomycin saline using a pulse lavage (Fig 1c).
Care is taken to eliminate free space in the container with saline and cotton pads to eliminate air as air causes dispersion of radiation. Specimen is taken to the radiotherapy department and as described earlier 50 Gy of single shot radiotherapy is given to the specimen after planning CT scan (Fig 2b,2c). This procedure takes between 30 – 90 minutes depending on the radiation machine used. The specimen is then brought back to the theatre and cleaned and washed with Vancomycin saline (Fig 2d).
The medullary canal of the sterilised bone can either be filled with bone cement or fibular graft to add on to the osteoconductive property (Fig 3a). The graft is re-implanted and stabilised by appropriate plate and screw fixation (Fig 3b). Care must be taken to put only minimal screws in the re-implanted graft during fixation. In case of tibial lesions an additional medial gastrocnemius flap may be needed for covering the sub cutaneous implants (Fig 3c). Post operatively the joint is mobilised immediately and weight bearing started as appropriate to the the fixation used. Patients are followed up at the routine frequency practised for malignant bone tumours. Radiological, oncological and functional assessment are done at each visit. The diaphyseal end takes more time to unite than the metaphyseal end. In our series of 16 patients who had undergone ECRT and reimplantation for malignant bone tumours of the extremity and had completed two year follow up, the metaphyseal end took an average of 6.2 months (4 – 12 months) for union while the diaphyseal end united in 10.6 months ( 5 – 15 months) (Fig 3c, 3d).
There were two cases of non union at the diaphyseal end for which subsequent bone grafting was required to attain union.
ECRT can also be used in reconstruction of bony defects after Internal Hemipelvectomy for malignant tumours of the pelvis. Here like in the long bones the tumour can be resected with margins as per the pre chemotherapy imagings and reimplanted after ECRT and fixed with appropriate plate and screw fixation (Fig 4a-d).
ECRT and reimplantation is an inexpensive method of reconstruction which can be carried out even in hospitals without radiation facility. The specimen after resection can be transported to the nearby centre having radiation facility where ECRT can be done and brought back and reimplanted. This method eliminates the need to have a tissue bank in hospital for doing biological reconstruction and also is not associated with the complications of using massive allografts. This technique also has the advantage that it provides an exact size matched graft for reconstruction.
If the tumour has caused extensive destruction of the bone or has a pathological fracture, it may be mechanically not sound to reimplant it after ECRT and alternative methods of reconstruction like intercalary implants or allografts would be ideal. Graft fracture is one complication that can occur in this procedure. This can be reduced by using appropriate fixation devices which bridge the whole length of the graft and also augmenting the graft with bone cement or fibular graft.
ECRT is an oncologically safe and mechanically stable procedure in biologically reconstructing bony defects after tumour resection. But the success of the procedure depends on appropriate patient selection, meticulous preoperative planning, implementing these plans intra operatively and the infrastructure backup to support it.
References
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2. Kotz, R.I.; Windhager, R.; Dominkus, M.; Robioneck, B.; Muller-Daniels, H. A self-extending paediatric leg implant. Nature 2000, 406, 143–144.
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Dr.Subin Sugath
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