Wilms’ tumor, also known as renal embryonal tumor, is the first among pediatric retroperitoneal tumors, accounting for 24-34% of cases. It is an embryonic malignant tumor containing a mixture of tissues, with the main lesion in the kidney. The main treatment measures are surgical resection, chemotherapy and radiotherapy, with surgical resection as the most basic means.
I. Clinical manifestations
(1) The disease should be considered when a painless mass is found on one side of the lower back of a healthy child. The surface of the mass is smooth, hard, with clear edges, and it can extend to the iliac fossa, but does not exceed the abdominal midline.
(2) The tumor may increase rapidly in size within one month or several months, accompanied by the appearance of cachexia symptoms.
(3) Most of them metastasize to the abdomen in the later stage.
(4) A few children have other malformations, such as no iris, hemiplegia and genitourinary tract malformation.
II. Clinical staging
The staging method of NWTS-3 (National Wilms’ Tumor Study Group) in the United States, which is commonly used now, is based on the distribution of tumors observed visually or microscopically.
Stage I: The tumor is confined to the kidney and can be completely resected. The renal envelope is intact and the tumor is not ruptured preoperatively or intraoperatively; no tumor remains in the surgical incision margin.
Stage II: The tumor extends outside the kidney but can be completely resected; perinephric invasion (e.g., the tumor has penetrated the perinephric membrane into the perirenal soft tissue); extrarenal vascular invasion or tumor thrombus formation; the tumor has been biopsied or there is localized leakage of the tumor but it is confined to the lateral abdomen; there is no tumor remaining at or beyond the surgical incision margin.
Stage III: Non-hematogenous dissemination of the mass confined to the abdomen. There are the following conditions.
1. there has been invasion of the hilar lymph nodes, the para-aortic lymphatic chain, or it has gone beyond the above.
2. the peritoneum is extensively contaminated with tumor cells preoperatively or intraoperatively.
3, the peritoneal surface has been implanted.
4, the mass has extended beyond the surgical margins when observed visually or microscopically.
5, local infiltration into vital organs that cannot be surgically removed intact.
Stage IV: hematogenous metastases beyond the scope of stage III lesions (e.g., lung, liver, bone, brain).
Stage V: involvement of both kidneys at the time of diagnosis; staging of each side of the tumor prior to biopsy according to the extent of lesions and with reference to the above criteria.
III. Diagnosis
(1) CT and MRI: It can clearly show the size of tumor and the scope of surrounding infiltration.
(2) Pathology: NWTS-1 (1981, 1982) combined clinical prognosis and pathological histological characteristics of Wilm’s tumor into two types: good prognosis histotype (FH) and poor prognosis histotype (UH). The good prognosis type includes: renal embryoblastoma and mesoblastic nephroma. The poor prognosis type includes: undifferentiated, clear cell sarcoma and rhabdomyosarcoma-like type. This type has a high recurrence rate and high mortality rate, and is prone to early lung, liver, brain and bone metastases.
(3) Other tests: abdominal ultrasound, etc.
(4) Puncture biopsy is generally not performed.
IV. Treatment principles
Early diagnosis is extremely important. For bilateral lesions, systemic chemotherapy is given first, and radiotherapy is then considered.
Stage I and II good prognosis type: surgery to remove the primary tumor, no local radiotherapy is needed after surgery, but chemotherapy is required after surgery. Combination chemotherapy with vincristine (VCR) + rejuvenomycin for 6 months (both VCR 1.5mg/M2/time iv, once a week and rejuvenomycin 15mg/kg/time iv x 5 times every 6 weeks. After 3 courses of chemotherapy, the treatment was changed to once every 12 weeks, and after 8 courses of vincristine, the treatment was stopped for 2 weeks and then once a week x 2 times, and then changed to once every 12 weeks, with each course including VCR once a week x 2 times.
Stage III good prognosis type: resection of the primary tumor, local radiotherapy 1080 cGy to the tumor bed on the 9th postoperative day, plus 1080 cGy for residual foci >3cm in diameter, the initial irradiation field should cross the midline, including the relevant vertebral body, but should avoid the contralateral kidney, including the para-aortic lymph nodes. The whole abdomen should be irradiated if the tumor has ruptured before surgery, tumor cell contamination at the time of surgery or extensive peritoneal involvement. Chemotherapy should be added with Adriamycin 60mg/M2/div every 12 weeks in addition to the combination of vincristine vincristine for 15 months.
Stage IV good prognosis type and clear cell sarcoma type in stage I-IV poor prognosis type: chemotherapy and radiotherapy regimen are the same as those in stage III, but for distant metastases, radiotherapy must be added according to the radiotherapy tolerance of the organs, lung: 1200 cGy, liver: 1980 cGy, bone or brain 3060 cGy.
Undifferentiated type in poor prognosis type: Stage I treatment is the same as stage I good prognosis type, stage II-IV treatment is the same as stage III good prognosis type, but add 3 days of cyclophosphamide 10mg/kg/day iv × 3 days to each course of adriamycin and vincristine, and add post-surgical radiotherapy. In rhabdomyosarcoma-like type, there is no ideal regimen, and the combination of pedialyte glycoside/cisplatin and pedialyte glycoside/isocyclophosphamide may be effective.
Stage V: (1) At the initial dissection, remove the tumor if all the tumor can be removed and sufficient functional kidney tissue can be preserved, or if this cannot be achieved, remove the severely involved kidney alone. (2) Then combine with vincristine and vincristine treatment, if the tumor still cannot shrink after one month of treatment, then add adriamycin or local radiotherapy, but the amount of radiotherapy should not be more than 1500 cGy (given within 11/2-2 weeks), and after 3-6 months, make the second dissection and remove the tumor of the less involved kidney, and save as many functional kidneys as possible during the operation. (3) Application of combined chemotherapy with adriamycin, vincristine and vincristine for 15 months.
1.Radiotherapy technique
Postoperative radiotherapy is mainly aimed at the tumor bed and suspicious area with metal clips, and usually starts after the incision heals about 10 days after surgery. Several NWTS studies have shown that although radiation therapy is not required immediately after surgery, the timing of treatment is critical. Patients who receive radiation therapy that is delayed by 10 days or more postoperatively have a significantly increased chance of abdominal recurrence, especially in UHWilms tumors. Because pathologists cannot quickly identify UH, all patients with Wilms tumors requiring radiotherapy should begin radiotherapy within 10 days of surgery. Although most patients do not require radiotherapy, for children, an appointment for radiotherapy can be made and then cancelled if postoperative tests show that radiotherapy is not needed.
According to NWTS-1 and NWTS-2, the dose of radiotherapy in the surgical bed should be determined according to the patient’s age, but no significant dose response was found. NWTS-3, a randomized study of patients with FH Wilms tumor, reported that radiotherapy should be given without radiotherapy for stage II FH, 10 Gy for stage III FH, and 12 Gy for stage IV FH lung irradiation. 12 Gy was given.
The data from NWTS-3 and NWTS-4 showed that intra-abdominal recurrence was rare in clear cell sarcoma and there was no dose response; intra-abdominal recurrence was significantly higher in interstitial tumors, but no dose response was observed, so a 10 Gy dose was given for all abdominal lesions.
A multifactorial Cox regression analysis of all factors contributing to abdominal recurrence was performed in the NWTS-1 report, which showed that a small irradiation field was significantly associated with abdominal recurrence (P=0.002). In contrast, no correlation was found between the two in the NWTS-3 report.
Tumors confined to the surgical site, even with tumor spillage, required only half-sided abdominal radiotherapy. The use of parallel to penetrating irradiation fields with 4-6 Mv photons is preferred.
The field of irradiation should include the tumor bed and a 1-3 cm border around the kidney. The inner boundary of the irradiated field must cross the midline and include the entirety of the vertebral body to minimize growth deformities. A tangential abdominal wall lead blocking technique can be used. In case of pulmonary metastases, total lung irradiation should be performed, using an irregular irradiation field to minimize surrounding normal soft tissue damage. For bilateral FHWilms tumor, the dose to one kidney should be limited to l0Gy.
2.Treatment efficacy
The 2-year recurrence-free survival rates for stage I, II, III and IV patients were 88%, 78%, 70% and 49%, respectively. For those with lymph node involvement at diagnosis, the relapse-free survival rate is lower, e.g., only 54% for those with positive lymph nodes and 82% for those with negative lymph nodes, and up to 90% for those with good prognosis and only 54% for those with poor prognosis.
The 5-year survival rate of reasonable comprehensive treatment is 60%.
3.Late complications of treatment
The effect of high-energy radiation therapy on the bone is common, but just like normal pressure radiation exposure, the degree is not as severe. Clinical data from Washington University in St. Louis, Missouri, USA, confirm a high incidence of scoliosis (14/26), but functional disability is rare.
The NWTS study of 2500 of over 40,000 patients with late complications showed that musculoskeletal abnormalities were more common in patients treated with radiation (61% of scoliosis compared to 9% in patients not treated with radiation), and the results also showed that the combination of adriamycin and radiation did not significantly increase the incidence of cardiac complications. The cumulative probability of second malignancy was 1.5%, and the risk was increased by abdominal radiotherapy. The risk was higher when 35GY was irradiated in combination with adriamycin.