Preface
In China, due to the lack of medical knowledge and the lack of the current medical system, many diseases cannot be detected early and treated in a standardized way, so the training of medical knowledge for patients and their families is an important way to improve the health of all people. Therefore, the establishment of an effective referral system is an effective way to improve the level of treatment and to achieve specialized treatment so that patients can receive standardized and effective treatment, thus improving the efficacy of treatment and benefiting patients.
The knee joint is the most common site of pain, especially in children and adolescents who are active, and pain in the joint is often attributed to sports injuries.
Because of the rapid growth of bones in this period, the pain caused by tumor is easily misdiagnosed as growing pains or thought to be general arthritis or sports injuries, etc. Parents seldom associate tumor with their children’s joint pains, and such minor pains are often neglected without parents’ attention, which delays the condition and misses the best time for treatment. If a teenager develops knee swelling, pain, increased skin temperature and limited joint movement, he/she should seek medical attention as soon as possible. The most basic thing is to take an X-ray of the joint area, and if it is not determined, a CT examination is needed, and it is best to seek a bone and joint tumor specialist to rule out tumors.
Osteosarcoma is the most common primary malignant bone tumor, which occurs in adolescents aged 10-25 years old and poses a serious threat to their lives. Osteosarcoma is usually found in the extremities and has a rapid development and short course, with early hematogenous metastasis. It is known that the incidence of sarcoma now occupies 15-20% of childhood tumors and 1% of adult tumors. The incidence of osteosarcoma is about 2/100,000, with a high degree of malignancy. 85%-90% of patients have clinically undetectable micrometastases at the time of consultation, and lung is the most common site of metastasis, accounting for about 90%.
Due to the lack of understanding of osteosarcoma by many lay doctors and parents, and the less obvious clinical symptoms in the early stage of the disease, 60% of the patients are already in the middle and late stage when they are diagnosed, and 50% of the patients are delayed because they cannot get timely diagnosis and standard treatment. 30%-40% of the patients with osteosarcoma have been misdiagnosed, and the misdiagnosis and mistreatment will make the disease progress.
The diagnosis of osteosarcoma should be a combination of clinical, imaging and pathology. The classification and diagnosis of osteosarcoma are extremely complex, and it is difficult to make a correct diagnosis by clinical examination and imaging alone. Incorrect biopsy or surgery is likely to deprive patients of the opportunity to preserve their limbs.
In the treatment of osteosarcoma, “many patients’ parents always hope to take conservative treatment and are afraid of chemotherapy, and look to TCM for treatment. TCM can only be used as an adjunct in the treatment of tumors, and proper application of TCM after surgery can achieve the effects of regulating qi and blood and enhancing immune function, but the effect is very limited. If we rely solely on the external and internal application of local traditional Chinese medicine as a “cure”, it will only delay the treatment time and eventually lead to the progression of the disease, lung metastasis and death. Chemotherapy is the most important treatment for osteosarcoma. Chemotherapy drugs can kill tumor cells in the body, cause tumor necrosis and kill micro-metastases. The model of preoperative chemotherapy + surgery + postoperative chemotherapy has been widely accepted.
Principles of osteosarcoma treatment.
1, the model of preoperative chemotherapy + surgery + postoperative chemotherapy has been widely accepted as the standard treatment model for osteosarcoma.
2.Limb preservation surgery has become the basic mode of treatment for osteosarcoma patients, and the preserved limb function is better than prosthesis, and amputation is recommended for those without limb preservation conditions.
3.Pulmonary metastases can be removed for those with combined single lung metastasis source.
4. Chemotherapy is recommended for patients with recurrence and metastasis. Combination of radiotherapy and chemotherapy is feasible for multiple metastases in the lung.
In bone tumor center, surgery combined with preoperative and postoperative chemotherapy can cure 60% to 70% of patients with osteosarcoma, and the surgical limb preservation rate is more than 90%], and the limb function is good after limb preservation; statistics found that 78% of patients have satisfactory limb function after limb preservation surgery.
Standardized comprehensive treatment is the key to cure osteosarcoma.
Osteosarcoma of the lower femur: limb swelling and activity limitation
Typical X-ray manifestations of osteosarcoma patients: see bone destruction, soft tissue mass shadow, tumor osteogenesis, periosteal reaction
Osteosarcoma of the lower femur, with sunray-like periosteal reaction shown by arrow
Imaging features of osteosarcoma
Symptoms of osteosarcoma
Adolescents are growing and may have growing pains. At the same time, adolescents are usually active and inevitably have bumps and bruises, and the pains are often not taken seriously as normal growing pains or sports injuries, but it is necessary to be alert to exclude the occurrence of tumors, especially unexplained joint pains around the knee joint.
Osteosarcoma mainly develops in the lower extremities above and below the knee joint, and is the most common primary bone tumor in adolescents, with high malignancy and rapid development. Early detection and standardized treatment is an effective way to improve the survival rate.
How to achieve early detection? In fact, there are always some symptoms in the early stage of the disease, if the following characteristics appear, you should go to the bone tumor specialist in time to achieve early detection.
At the early stage of the disease, the affected limb often has irregular hidden pain and discomfort, which is intermittent pain, soreness and dull pain around the joint at the beginning, which is effective with painkillers;
2.Pain not related to movement, “night pain” is obvious, because pain at night is the manifestation of tumor growth; joint pain is aggravated when movement.
3. Gradually, swelling and lumps around the joints appear, accompanied by increased skin temperature and angry veins. The lump keeps increasing and the symptoms become more and more aggravated;
4.The course of the disease develops very rapidly, and even aggravates every other day. In addition, some patients with osteosarcoma may have a very rapid development of the disease, and the disease may worsen even every other day.
In addition, some patients with osteosarcoma may have systemic reactions such as elevated body temperature, anorexia, emaciation and pallor. If the correct diagnosis is made at the early stage of the disease and the treatment is standardized, the treatment effect is also better and the survival time of the child can be significantly extended.
The tumor grows rapidly without standardized treatment, and the chance of limb preservation is lost.
Chinese medicine treatment fails to control the development of the disease, and the chance of treatment is lost forever.
Correcting misconceptions about osteosarcoma
In the past 30 years, the use of neoadjuvant and adjuvant chemotherapy has dramatically improved the survival rate of patients with osteosarcoma. In bone tumor centers, surgery combined with preoperative and postoperative chemotherapy can cure 60% to 70% of patients with osteosarcoma, with a surgical limb preservation rate of over 90%], and good limb function after limb preservation; statistics found that 78% of patients had satisfactory limb function after limb preservation surgery. The aim of treatment has shifted from saving the patient’s life to limb-preserving treatment and preserving the function of the limb with emphasis on the patient’s survival quality, and limb-preserving treatment for osteosarcoma has become the mainstream of treatment. However, there are still many misconceptions in the understanding of osteosarcoma.
Myth 1: Osteosarcoma is incurable cancer
Although we have made great progress in the treatment of malignant tumors, there are still a lot of problems, most of the tumor patients have not been diagnosed and treated at an early stage, their disease is late, treatment is difficult and survival period is short. However, in the past 30 years, due to the application of neoadjuvant chemotherapy, the survival rate of patients with malignant bone tumors has been significantly improved. Overseas, the 5-year survival rate of patients with osteosarcoma has been reported to reach 60%-75%, and even the 5-year tumor-free survival rate has reached 80%. Therefore, as long as early detection and standardized treatment, osteosarcoma can be completely controlled or cured.
Myth 2: Amputation is the only option for osteosarcoma patients
Historically, amputation was once the standard treatment for osteosarcoma, and only 10% to 20% of patients treated with this method survive long-term, with most patients dying of pulmonary metastases within 2 years. 85% to 90% of patients with osteosarcoma already have clinically undetectable micrometastases at the time of consultation, with the lung being the most common site of metastasis, accounting for about 90%. Therefore, even if a high level amputation is performed at the first time of diagnosis, it cannot control the recurrence of tumor and distant metastasis in the amputated stump; that is, amputation alone is not beneficial to improve the survival rate of patients with osteosarcoma. More than 50% of patients developed metastases within 6 months of diagnosis, more than 80% of patients developed tumors again within 2 years of diagnosis, and about 20% of patients survived tumor-free with surgery alone. The application of neoadjuvant chemotherapy and adjuvant chemotherapy has greatly improved the survival rate of patients and has provided favorable conditions for the development of limb preservation techniques, and surgery combined with preoperative and postoperative chemotherapy can cure 60% to 70% of patients with osteosarcoma, with a surgical limb preservation rate of over 90%].
Multicenter studies have confirmed that limb preservation therapy does not affect the overall survival rate of patients, and there is no significant difference in survival rate and tumor local recurrence rate between patients treated with limb preservation and those who underwent radical amputation. In most oncology treatment centers, more than 80% of patients are now treated with limb preservation therapy.
Myth 3: The earlier the surgery for osteosarcoma patients, the better
Preoperative chemotherapy can cause tumor necrosis and also reduce the size of the tumor and eliminate the tiny satellite foci in the tumor response area, all of which increase the feasibility and safety of limb-preserving surgery. Several studies have shown that the rate of tumor necrosis within the resected specimen is a very effective prognostic factor. The current course of treatment for osteosarcoma is preoperative multi-drug combination chemotherapy (total of 6 to 18 weeks) followed by resection of the tumor and postoperative adjuvant chemotherapy. Because studies have shown that a good histologic response after preoperative chemotherapy is closely associated with improved prognosis for patients with tumors, the survival rate of patients with malignant bone tumors has improved significantly over the past 30 years, largely due to neoadjuvant chemotherapy. the concept of neoadjuvant chemotherapy was introduced by Rosen in 1982 and has been widely accepted as an important milestone in the history of osteosarcoma treatment.
Myth 4: Fear of chemotherapy
Many people are afraid of chemotherapy because of the unfamiliarity with malignant tumors and chemotherapy. With the progress of clinical research on chemotherapy in the past 30 years, the status of chemotherapy in tumor treatment has become irreplaceable, and chemotherapy, surgery and radiotherapy have become the three main means of tumor treatment, and the toxic side effects of chemotherapy drugs on most organs are mild and reversible. With advances in supportive therapy, such as granulocyte colony-stimulating factor and central antiemetics, high-intensity chemotherapy has become fully tolerable.
The treatment of osteosarcoma has formed a standardized model in bone cancer centers, and the model of preoperative chemotherapy + surgery + postoperative chemotherapy has been widely accepted, and the close cooperation between patients and their families and oncologists to get standardized scientific treatment is an effective way to improve the efficacy.
Mastering the indications for limb preservation in osteosarcoma.
Mastering the indications for limb preservation and selecting patients with limb preservation conditions for limb preservation treatment is an important step in the process of osteosarcoma treatment and a guarantee to achieve good efficacy of limb preservation treatment.
I. Indications for surgery.
1.The patient’s epiphyseal growth and development has basically matured, and the age is preferably >15 years old;
2, Enneking surgical stage IIA, stage IIB patients, such as good response to chemotherapy, can also be considered;
3.No major vascular nerve involvement, pathological fracture, local infection and diffuse skin infiltration;
4.The tumor can be removed completely outside the tumor;
5.The function of the preserved limb is expected to be better than that of the prosthesis;
6.The local recurrence rate of limb preservation surgery will not be higher than amputation, and the expected survival rate will not be lower than amputation;
7.The patient and family members have the desire to preserve the limb.
II. Relative indications
1.Pathological fracture of tumor, bone formation of fracture end after chemotherapy, tumor necrosis forming package;
2. Children and adolescents with immature epiphysis can be replaced with extendable prosthesis if necessary.
C. Absolute anti indications.
1.Tumor is too big to erode to extra-bony tissues for large block resection.
2.Vascular nerve is wrapped by the tumor;
Limb preservation surgery methods.
1.Tumor segment inactivation and re-transplantation;
2.Tumor-based artificial joint prosthesis replacement;
3.Homogeneous composite prosthesis;
4.Fibula graft with vascular tip
5. Allograft arthroplasty;
6.Joint fusion.
Treatment strategy of osteosarcoma
Osteosarcoma is the most common primary malignant tumor of bone and is a highly malignant mesenchymal tissue tumor that occurs in adolescents between the ages of 10 and 20. Osteosarcoma grows aggressively locally and is prone to metastasis. Amputation was once the standard treatment for osteosarcoma, but only 10%-20% of patients survive long term after amputation, and most die of pulmonary metastases within 2 years. 85%-90% of patients have clinically undetectable micrometastases at the time of presentation.
Since the 1970s, many scholars have carried out adjuvant chemotherapy and neoadjuvant chemotherapy in combination with multiple drugs. Under the integrated treatment of effective chemotherapy and surgery, the treatment effect of osteosarcoma has been improving, and the five-year tumor-free survival rate has increased from 15% to 20% in the past to 60% to 80%, and the establishment of chemotherapy in the treatment of osteosarcoma has improved the 5-year survival rate of osteosarcoma patients and promoted the development of limb preservation technology. In addition, inactivation and replantation of tumor segments, allograft bone, composite artificial joints, and tumor-based prosthesis have replaced amputation. Nevertheless, there is still a significant gap between the cure rate of osteosarcoma in China and advanced foreign countries because some orthopedic surgeons have not mastered the principles of standardized and comprehensive treatment, as well as the huge economic expenses incurred by the treatment and the unbearable side effects of chemotherapy for patients, resulting in their inability to complete the entire treatment course.
The diagnosis of osteosarcoma is not very difficult for experienced orthopedic oncologists, but should be highly alert for cases with atypical performance. On typical X-ray films, it usually appears as a mixed lesion with both osteolysis and osteogenesis, with indistinct margins of the lesion, the cortex is usually destroyed, periosteal reaction can be seen, and the tumor invades the soft tissue to form a mixed ossified mass. When the clinical and imaging manifestations of the lesion suggest a more typical osteosarcoma, puncture or excisional biopsy is often used to confirm the diagnosis.
The preoperative staging of the tumor is also very important. The surgical staging system proposed by Enneking is widely used and has a good correlation with the prognosis of the tumor. Preoperative examinations include: X-ray of the tumor site, CT, MRI, whole body bone scan, lung CT, and hematological examinations, including alkaline phosphatase, which are not interchangeable and have different significance in tumor diagnosis.
Rosen proposed the concept of neoadjuvant chemotherapy in 1982, and the concept of chemotherapy is as follows.
(1) Early chemotherapy can kill small metastases, avoiding the delay of surgery and blood transfusion to reduce the body’s resistance and promote the growth of metastases;
②Killing the primary foci is beneficial to the limb preservation surgery;
③Evaluate the effect of preoperative chemotherapy, adjust the postoperative chemotherapy regimen and judge the prognosis. Adriamycin, cisplatin, isocyclophosphamide and high-dose methotrexate are the most commonly used drugs in chemotherapy for osteosarcoma, and many scholars have conducted extensive and in-depth studies on these drugs. When these drugs are used alone, the response rate is only close to 30%, whereas when they are combined in high doses, synergistic effects can be created between the drugs, potentially resulting in 100% tumor necrosis in vivo.
Currently, the following chemotherapy regimens are commonly used internationally: Rosen’s T7, T10, T12, T19, T20 series, and HD-MTX-CF-ADM-CDDP combination therapy, Jeffe’s TIOS (treatment and investigation of osteosarcoma) chemotherapy regimen, Coss ‘s protocol (a collaborative German-Austrian study group on osteosarcoma chemotherapy), the Rizzoli Institute’s chemotherapy protocol (Bacci), the CCG7921 study protocol designed by the CCG (Children’s Cancer Group) in 1993 (with the new addition of Ifosfamide isocyclophosphamide). Arterial infusion chemotherapy does not improve long-term survival of patients compared to intravenous chemotherapy, which has been reported to be worse, and is aimed at targeting micro-metastases in the lung and improving long-term survival of patients.
Assessment of chemotherapy efficacy: Clinical manifestations of excellent response to chemotherapy are pain relief, reduced swelling, decreased alkaline phosphatase levels, and healing of pathological fractures; X-ray manifestations are increased calcification within the tumor bone-like stroma, marked periosteal thickening, reossification, and marked sclerosis around the tumor, which is manifested on CT as a ring of calcification (calcified periosteum) around the perimeter of the tumor, a phenomenon that indicates pseudo-envelope within the obvious necrosis within the pseudo-envelope of the tumor. If there is a pathological fracture, the fracture will begin to heal in the presence of a good response to chemotherapy. It is more scientific to assess the degree of tumor necrosis after chemotherapy.
Preoperatively, limb-preserving surgery is performed after completion of 4 to 8 cycles of chemotherapy. If the necrosis rate is greater than 90%, the original chemotherapy drug should be used for postoperative chemotherapy; if the necrosis rate is less than 90%, postoperative chemotherapy should be modified by increasing the chemotherapy drug and dose as well as extending the chemotherapy time to improve the effectiveness of chemotherapy. effectiveness.
The main role of postoperative chemotherapy is to prevent tumor metastasis. It should be noted that there is no evidence from prospective studies to demonstrate a significant difference in patient survival at five years between neoadjuvant chemotherapy and conventional postoperative chemotherapy. Also, there is no evidence of a significant difference in long-term survival between patients treated with preoperative chemotherapy by the arterial route compared to the intravenous route.
The standard adjuvant chemotherapy is a predetermined regimen of chemotherapy after osteosarcoma surgery, usually starting about 1 week after amputation and 2 to 3 weeks after limb preservation, with a total course lasting about 1 year. To achieve good efficacy, chemotherapy for osteosarcoma should follow the principles of adequate drug doses, cyclic dosing, long maintenance of blood concentrations in the safe and effective range, adequate rest during the interval between doses, and protection of the bone marrow. Due to the high doses used, attention should be paid to the prevention and control of chemotherapy side effects in patients to avoid the risk of patient death due to chemotherapy side effects.
In the past 30 years due to the use of neoadjuvant chemotherapy and adjuvant chemotherapy, the survival rate of patients with osteosarcoma has been dramatically improved. In bone tumor centers, surgery combined with preoperative and postoperative chemotherapy can cure 60% to 70% of patients with osteosarcoma, and the surgical limb preservation rate is over 90%. The development of reconstruction technology and the improvement of surgical techniques and experience of orthopedic oncologists have gradually increased the success rate of limb preservation surgery, and after limb preservation surgery The success rate of limb-preserving surgery has gradually increased, and the limb function after limb-preserving surgery is good; statistics found that 78% of patients have satisfactory limb function after limb-preserving surgery. The aim of treatment has shifted from saving the patient’s life to limb preservation treatment and limb function preservation, which emphasizes the quality of patient’s survival, and limb preservation treatment for osteosarcoma has become the mainstream of treatment.
It should be noted that the most critical aspect of limb preservation surgery is tumor cutting rather than reconstruction. Failure to remove sufficient bone length as required, or failure to remove the tumor outside the soft tissue compartment, will severely compromise the patient’s local recurrence and survival rates. Surgical resection to achieve a tumor-free surgical border is a very important principle. Since the outcome of local recurrence is fatal, adequate local control of the tumor should be achieved when performing limb-sparing surgery. If an extensive surgical border can be achieved, the tumor-free survival and overall survival of amputated and conserved patients are similar.
It is very important to correctly identify the indications for limb preservation, and the surgical approach chosen should first be able to remove the tumor completely. Forced limb preservation without limb preservation is the most common misconception in limb preservation surgery for osteosarcoma in China, and limb preservation for the sake of limb preservation leads to inevitable residual tumor. The trade-off between limb preservation and amputation should be made. There are many methods of limb preservation surgery, which can be selected according to the patient’s tumor site, tumor size, general condition, soft tissue condition, economic condition, doctor’s skill and experience, and hospital condition.
Limb preservation surgery alone without regular chemotherapy is not effective for the lives of most patients with osteosarcoma. The limb preservation should be based on complete chemotherapy. If the limb is preserved and the patient cannot afford the subsequent chemotherapy, the previous work will be abandoned and the tumor will eventually metastasize distantly. A non-functional limb is not the goal pursued by limb preservation surgery for osteosarcoma, and a limb with tumor residual will eventually fail to be preserved. Therefore, amputation is still one of the main surgical procedures for the surgical treatment of osteosarcoma when limb preservation is not eligible or cannot be performed due to hospital conditions or patients’ economic restrictions.