Adolescents are the most vigorous and energetic stage of life, and they like to engage in various sports and are most vulnerable to trauma. Pain and soft tissue swelling in the limbs are often considered by many children and parents to be caused by growing pain or trauma, and often do not attract much attention, unbeknownst to them, osteosarcoma is prone to occur at this stage of adolescence. In addition, due to the uneven level of treatment in different medical institutions, patients cannot receive timely and appropriate treatment.
What is osteosarcoma? What is the incidence of osteosarcoma?
Osteosarcoma, also known as osteogenic sarcoma, is the most common malignant tumor that originates in bone and has a high degree of malignancy, rapid progression and easy metastasis. It is highly malignant, rapidly progressive and easily metastatic. It accounts for approximately 4.4/million new cases per year in children and adolescents aged 0-24 years, or about 5% of all malignancies in children and adolescents.
Where do osteosarcomas most commonly occur?
About half of all osteosarcomas occur around the knee, which is the upper calf and lower thigh. The rest can occur in the upper extremity, upper femur, iliac bone, spine, etc. Very few occur in the soft tissues and internal organs. Overseas statistics have shown that more than 1/5 of patients are found to have distant metastases at the time of consultation, with lung metastases being the most common. Early detection of tumor and timely medical treatment can reduce the chance of metastasis and improve the outcome.
What are the manifestations of osteosarcoma?
Pain is an early symptom of osteosarcoma, which may occur before the appearance of tumor, initially as intermittent pain, gradually turning into continuous severe pain, especially more serious at night. Tumors with high malignancy have earlier and more severe pain, and often have a history of local trauma.
The soft tissues of the primary site are obviously swollen, with varying hardness and pressure pain, and the skin surface is mostly dilated with veins, and the local temperature is high. The whole body health gradually declines to failure, and patients with lung metastasis may also have corresponding metastatic symptoms such as cough and chest pain.
Therefore, the occurrence of pain and swelling in the extremities, regardless of the history of trauma, should not be taken lightly and should be seen promptly.
How to diagnose osteosarcoma?
The diagnosis of osteosarcoma must be made by pathological diagnosis. Biopsy methods include needle aspiration biopsy and surgical open biopsy, provided that sufficient amount of tumor tissue is obtained. The access for puncture and excision must take into account the possible limb preservation surgery and should be included in the incision for later limb preservation surgery. Therefore, biopsy should preferably be performed in a hospital with experience in osteosarcoma treatment so that inappropriate incisions will not affect the subsequent surgery.
Relevant laboratory and imaging tests should also be performed, including serum alkaline phosphatase (AKP) and lactate dehydrogenase (LDH), CT of the chest, CT or MRI of the primary site, whole-body bone scan, and PET-CT if available, in order to accurately assess whether there are distant metastases or jumping lesions.
What is the treatment outcome of osteosarcoma?
Prior to the 1970s, treatment consisted mainly of surgical removal of local lesions and amputation, but still more than half of the patients developed metastases within 6 months of diagnosis, 90% of the patients recurred within 2 years, and the survival rate did not exceed 20%. Starting from the 1970s, with the change of treatment concept and the progress of chemotherapeutic drugs, chemotherapy was used for the routine treatment of osteosarcoma and achieved significant efficacy. The concept of neoadjuvant chemotherapy was gradually developed from the late 1970s to the early 1980s, i.e., preoperative application of chemotherapy to treat small metastases while controlling the primary tumor foci to facilitate limb preservation and reduce the local recurrence rate, and postoperative chemotherapy regimens were adjusted according to the clinical, imaging and pathological histological response of osteosarcoma to chemotherapy. The surgical approach is gradually changing from radical amputation to various limb-preserving procedures. Due to the wide application of preoperative and postoperative chemotherapy with clinical use, the limb preservation rate after comprehensive treatment can reach 90%, and the 5-year survival rate can reach 50%-80%. For patients with metastases at the time of diagnosis, the survival rate has increased from less than 20% to about 40%. This shows that preoperative and postoperative high-dose combination chemotherapy is the main reason for the improved survival and limb preservation rates in osteosarcoma.
What factors can affect the prognosis of osteosarcoma?
1. The prognosis of osteosarcoma occurring in the distal limb is significantly better than that of osteosarcoma occurring in the proximal limb, and the prognosis of cases occurring in the median bone is the worst.
2. The larger the tumor, the worse the prognosis, and the prognosis of those with high lactate dehydrogenase before treatment is poor.
3. The prognosis of those with metastasis at the time of diagnosis is poor.
4. The prognosis of those with postoperative residuals is poor.
5. The higher the rate of tumor necrosis after neoadjuvant chemotherapy, the better the prognosis.
Once diagnosed, what are the principles of treatment for osteosarcoma?
Successful treatment includes effective systemic chemotherapy and complete resection of the lesion. Systemic chemotherapy includes preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy. Treatment should be effective in protecting the weight-bearing bone from pathological new fractures that could compromise limb-preserving surgery.
Should amputation or limb preservation be chosen? Which surgical procedure is more effective?
The choice of limb preservation or amputation in the surgical treatment of osteosarcoma is a practical issue faced in the treatment of osteosarcoma. However, it needs to be clear that preservation of life is the main purpose, basic principle and fundamental issue of treatment for osteosarcoma, as well as the minimum requirement for treatment. Life preservation is absolute, and limb preservation and amputation are relative. Preservation of limb and amputation are only two types of surgical options based on the preservation of life.
Since most osteosarcoma patients have tumors involving surrounding muscles and soft tissues, extensive resection is not possible, so most of the previous osteosarcoma surgeries were performed by amputation, mostly by super-articular amputation, such as tibial osteosarcoma from the middle and lower third of the femur, and osteosarcoma of the femur by hip joint dissection. However, it should be noted that amputation is not necessarily a radical resection.
With the advancement of chemotherapy, some patients can have all or part of the affected muscle or soft tissue tumor killed by effective chemotherapy, allowing for extensive resection and reconstruction, resulting in a significant increase in the number of patients who can undergo limb-sparing surgery. Statistics from many domestic and international medical institutions show that the survival rate of limb-preserving surgery is not significantly improved compared to amputation, but limb-preserving surgery can significantly improve the quality of survival and self-confidence of patients to return to society. The disadvantage of limb-preserving surgery is that there are more postoperative complications than amputation surgery, and the domestic literature reports that various complications amount to 40% to 50%.
Which patients are suitable for limb preservation surgery?
With the development of reconstructive technology and the improvement of surgical skills and experience of orthopedic oncologists, limb-preserving treatment has become the mainstream trend in the surgical treatment of osteosarcoma. However, not all patients with osteosarcoma can choose limb-preserving surgery, and certain indications are required. For example, cases where the tumor can reach the surgical margin without tumor residue and distant metastasis according to the comprehensive assessment of imaging and so on can be considered for limb-preserving surgery; it is estimated that the function after limb-preserving surgery should be stronger than the installation of prosthesis after amputation; the surgeon has rich experience, familiar with the principles of bone tumor surgical staging and resection, and has good reconstructive techniques and conditions; physically and economically can bear the high dose of preoperative and postoperative The surgeon is familiar with the principles of surgical staging and resection of bone tumors and has good reconstructive techniques and conditions; physically and financially able to tolerate preoperative and postoperative high-dose chemotherapy, because preoperative neoadjuvant chemotherapy is a prerequisite for limb preservation surgery; pathological fracture at diagnosis or during treatment is not a contraindication to limb preservation treatment, provided that the tumor can be extensively resected. Age is also one of the factors affecting limb preservation surgery. Patients of young age, especially those with primary lower limbs, are not advocated for limb preservation because postoperative growth and development can cause limb inequality and affect the quality of survival.
What are the current types of limb-sparing surgeries?
There are many types of limb preservation surgeries reported in the literature, and the main methods currently used are artificial prosthesis replacement, autologous or (and) allogeneic bone grafting and tumor segment bone inactivation and reuse.
What are the advantages and disadvantages of each type of limb preservation surgery?
(a) Artificial prosthesis replacement: It can achieve better early clinical results, restore the function of the affected limb immediately after surgery, with few early complications, and without worrying about fracture and non-union, and is suitable for tumors around the proximal femur and knee joint. Tumors of the humeral head and proximal humerus have also been widely used. Conventional artificial prosthesis, special artificial prosthesis and combined prosthesis are commonly used. However, there are many problems with the material, design and process of domestic prosthesis, and it is difficult to popularize the imported prosthesis in China because of its high price. Moreover, most of the bone tumor patients are young patients, if they can survive for a long time, their long term loosening and other problems should be considered.
(B) Autologous or (and) allogeneic bone and joint transplantation: including autologous fibula and clavicle transplantation with or without blood vessels, allogeneic large segment bone and bone and joint transplantation, which is a biologically active arthroplasty to restore bone continuity and reconstruct joint structure. The advantages of allogeneic bone grafts are the ability to restore bone volume and provide soft tissue attachment sites. Allogeneic bone has the advantages of wide source and convenient use, but the problems of rejection reaction, infectious toxic diseases and matching difficulties remain unsolved in China because the system of bone banking is not yet perfect.
(iii) Tumor segment bone inactivation and reuse: using tumor segment bone for reconstruction can avoid allogeneic bone graft and artificial joint replacement and the complications caused by them. There are more domestic researches in this area, which can be broadly divided into two types: (1) in vitro inactivation and replantation: the tumor segment bone is cut off, and the tumor cells are inactivated in vitro by alcohol, radiotherapy, freezing, boiling, etc., and then the tumor segment bone is replanted and fixed in the original place; (2) in vivo in situ inactivation: after the tumor segment bone is exposed, the tumor segment bone is not cut off and kept in situ, and then the tumor segment bone is inactivated by microwave and radiotherapy. (2) in situ inactivation: after the tumor segment bone is exposed, the tumor cells in the tumor segment bone are inactivated by microwave and radiotherapy without truncating the bone and keeping it in place. The advantages of tumor segment bone reuse are: simple surgery, low cost, no need to consider bone matching, which is more suitable for China’s national conditions, especially for young patients with long survival time, and the inactivated tumor cells can play an immune role. However, the greatest shortcoming is the susceptibility to pathological fracture and difficulty in healing during the process of bone reconditioning.
What complications are likely to occur in limb preservation surgery?
(a) Infection: It is the most dangerous complication after limb preservation surgery, and once it occurs, most cases still require amputation. Infection after limb preservation surgery often occurs 1 to 3 months after surgery, with an infection rate of about 10% (slightly higher for allograft bone grafts).
(b) Bone non-union: Commonly seen in cases of allograft bone graft and inactivated reimplantation of tumor bone. The non-healing rate of allogeneic hemiarthroplasty was reported to be around 11% in the early stage, and the non-healing rate of the connection of inactivated reimplantation of tumor segment bone was also around 10%. With in situ inactivation of the tuberous bone, there is no need to worry about non-healing. The treatment of nonunion of allograft bone graft and tumor segment bone inactivation replant is also relatively easy, and most of them can obtain satisfactory results with reimplantation and internal fixation.
(iii) Graft fracture: It is another common complication after limb preservation surgery. In particular, the incidence of allograft fractures can reach 16% to 19%, and generally occur 1 to 2 years after surgery. The treatment of fracture can be treated by various methods such as bone grafting, internal and external fixation and prosthesis replacement, and most of them can achieve more satisfactory results.
(D) fracture and loosening of artificial prosthesis: With the prolongation of survival of patients with osteosarcoma after limb preservation, the incidence of fracture and loosening of prosthesis increases year by year, and the loosening rate of 5 years is reported to be between 20% and 25% abroad. The management of this complication is to perform revision surgery of the artificial prosthesis.
Is chemotherapy for osteosarcoma effective?
A large number of clinical data show that a large amount of tumor necrosis can be seen on pathological examination after osteosarcoma surgery, with many specimens having a tumor necrosis rate of 90% or more. It is due to the widespread use of chemotherapy that the survival rate of osteosarcoma has increased from less than 20% to the current 50-80%, and the limb preservation rate has reached nearly 90%. Therefore, chemotherapy for osteosarcoma occupies an important place in the treatment and has become the standard of care.
Is high-dose chemotherapy for osteosarcoma dangerous?
Both preoperatively and postoperatively, high-dose strong chemotherapy is used for osteosarcoma, such as high-dose methotrexate, cisplatin, anthracyclines, isocyclophosphamide, etc. The side effects of chemotherapy with these drugs are strong, such as severe bone marrow suppression combined with infection, bleeding, gastrointestinal reactions, and damage to multiple organ functions such as heart, liver, and kidney, etc. Patients will suffer greater pain and burden physically, mentally, and economically. Each drug has different characteristics in use, such as hydration, alkalinization, detoxification, and supportive therapy, etc. It is important to receive chemotherapy under the guidance of an experienced physician to minimize the side effects and risks that patients experience.
Why should preoperative neoadjuvant chemotherapy be implemented?
Pre-operative neoadjuvant chemotherapy is a prerequisite for limb-preserving treatment and has guiding significance for post-operative chemotherapy.
(a) Effective neoadjuvant chemotherapy can necrotize a large number of tumor cells and shrink the tumor, which obviously improves the rate of limb preservation and reduces the chance of postoperative recurrence.
(ii) It can control micro metastases and blood type dissemination and reduce the chance of metastasis.
(iii) The tumor necrosis rate is used to evaluate the sensitivity of tumor to chemotherapeutic drugs, which helps the selection of postoperative chemotherapy regimen.
(iv) To make the tumor cells less active and reduce the chance of tumor cells spreading during surgery.
(v) The risk of neoadjuvant chemotherapy is that it can increase the possibility of tumor progression and metastasis during chemotherapy for patients who are ineffective in chemotherapy.
Do I still need chemotherapy after surgery?
Adjuvant chemotherapy after surgery is necessary to remove any microscopic lesions that may remain in the body and reduce the chance of recurrence and metastasis. If the pathology shows more than 90% tumor necrosis, the preoperative chemotherapy regimen can still be used after surgery, but in less than 90% of cases, the regimen needs to be changed.
Is radiotherapy effective for osteosarcoma?
The literature reports that normal doses of external irradiation have limited effect on osteosarcoma, but some results have been reported with intraoperative extra-large doses of radiotherapy without inactivating the tumor segment bone in vivo. Normal-dose radiotherapy can be considered for the treatment of metastases or palliative treatment for symptom relief.
In conclusion, osteosarcoma is a common malignant tumor in children and adolescents with a high degree of malignancy, but if detected early and treated with standardized comprehensive treatment, most patients can not only survive for a long time but also may retain their limbs to obtain a better quality of life. Regardless of whether there is trauma or not, parents should seek medical attention as soon as they find pain and swelling in their children’s limbs to facilitate early detection of osteosarcoma.
Because the treatment process of osteosarcoma is more complicated, limb preservation surgery is more difficult, and irregular treatment can affect the limb preservation rate and survival rate of patients. Therefore, once osteosarcoma is suspected, one should visit a hospital with treatment experience to receive standardized diagnosis and treatment.