Medulloblastoma (MB) is a common malignant tumor in children. It is a malignant and invasive embryonic tumor that occurs in the cerebellum or fourth ventricle and accounts for 12–25% of all CNS tumors. The main treatment of medulloblastoma is surgery. Postoperative radiotherapy can significantly reduce the recurrence and prolong the survival rate of patients. A recent study has shown that supine position for CSI was found to have similar survival outcomes compared with the prone position.A multicenter study found that modern radiotherapy techniques can enhance the dose uniformity in the target area, especially the spinal cord target area . However,there is little research on survival related to technology. Our study found that the IMRT radiotherapy dose of spinal cord recurrence was only 1 case, while the 3DCRT group had a relatively high recurrence rate of 3 cases. A number of other studies have found that [8, 9], IMRT and VMAT overlap planning design allows for more positioning errors, which may be another advantage of IMRT in craniospinal irradiation. This is different from the pattern of recurrence after proton radiotherapy. One study found , the rate of extracranial recurrence, especially spinal cord recurrence, was higher after proton radiotherapy. However, our study suggested that the rate of spinal cord recurrence and metastasis after IMRT radiotherapy for medulloblastoma was very low. The previously reported incidence of vertebral metastasis is not high . Our study suggests that vertebral metastasis is not uncommon, and various imaging techniques such as MR and PET-CT can play a role in diagnosis.
It was found that the following factors are important in rate of survival: radiotherapy technique, time interval between surgery and radiotherapy, assessment of pre-radiotherapy, chemotherapy intervention.
Firstly,whole brain and spinal cord technique is safe and feasible to use whole brain field irradiation. One study found , the application of left and right brain field in the whole brain and spinal cord was effective for penetrating irradiation, and only 1 of the 76 patients with 3D-CRT technology developed the failure of the sieve plate area. However, our study found that 2 out of 36 patients with medulloblastoma developed frontal lobe metastasis, which was considered as a possible failure of the sieve plate area. With the progress of radiotherapy technology, especially the development of VMAT and TOMO program for the treatment of whole brain and spinal cord technology [11, 12], the dose distribution in the target region was more uniform than that of 3DCRT and IMRT.
Secondly,whether the time interval between surgery and radiotherapy affects prognosis is still controversial.Del Charco indicated that the 5-year local control rate of < 45 days was 89%, while that of > 45 days was only 68%. And another study had shown that early postoperative radiotherapy could even be harmful. The 5-year PFS was 0%, 85%, and 75%, respectively, for intervals from surgery to radiotherapy of < 3 weeks, 3–5 weeks and ≥ 6 weeks was 0%, 85%, and 75%, respectively. Our study found that the PFS was significantly shortened when the interval time between surgery and radiotherapy was more than 12 weeks, suggesting that the interval time between surgery and radiotherapy for medulloblastoma should not be more than 12 weeks at the latest.
Thirdly,radiotherapy is an important part of the comprehensive treatment of medulloblastoma. The presence or absence of postoperative residual and spread is an important factor affecting the prognosis . The prognosis of patients is poor when it is disseminated and planted along the cerebrospinal fluid. According to the different states of Chang's staging system before radiotherapy ,the patients were divided into stage M0 - stage M4. M0: no tumor metastasis was found;M1: only tumor cells were found in cerebrospinal fluid;M2: tumor cells are confined to the brain;M3: presence of CSF metastasis;M4: there are distant metastases outside the nervous system. The survival conditions were markedly different from period to period. Our study also found that the survival of the non-disseminated group (M0) was the best, while the survival of the partial residual group (M2) and the CSF disseminated group (M3) was poor. Since all the patients in this study were aged ≥ 3 years, the M0 group was the low-risk group, while the M2 groups and the M3 groups were the high-risk groups. Modern installments have been added to molecular biology's classification in a more refined way , and molecular typing was not studied in this study due to the defects of the samples.
Lastly,Postoperative chemotherapy is an important part of the comprehensive treatment of medulloblastoma, and a number of studies have suggested that postoperative chemotherapy can improve the survival of patients with medulloblastoma [18, 19]. Research from National Cancer Data Base shown that, the 5-year survival rate of the adjuvant chemotherapy group was significantly higher than that of radiotherapy alone, which was 86.1% and 71.6%, respectively. Recent research suggests that preoperative chemotherapy can also yield survival benefits .In terms of the choice of chemotherapy regimen, the combination of three drugs may be more effective ,lomustine(CCNU), cisplatin, and vincristine or cyclophosphamide, cisplatin, and vincristine are more commonly used.Our study indicated that there was no statistical difference in PFS and OS in the chemotherapy group,the chemotherapy-free group,the EP chemotherapy group and the TMZ chemotherapy group. Our study also clarified that single drug or double drug combination chemotherapy could not make patients with medulloblastoma benefit from postoperative chemotherapy.
Multivariate Cox regression analysis showed that recurrence, residual or spread before radiotherapy was an independent prognostic factor affecting PFS.This also explained, to some extent, the significant shortening of PFS in patients with medulloblastoma more than 12 weeks after surgery and radiotherapy, which may be due to the increased proportion of local recurrence or spinal cord dissemination due to the extended interval, thus affecting the disease-free survival of patients. However, radiotherapy is a negative correlation factor, indicating that IMRT technology can reduce the negative survival effect caused by recurrence spread to a certain extent.
In summary, IMRT technology has advantages over 3D-CRT technology in total cerebral spinal radiation, especially the lower spinal cord recurrence rate. The interval time between surgery and radiotherapy should be no more than 12 weeks.PFS and OS were higher in patients without residual, recurrence and spread before radiotherapy. Chemotherapy with TMZ alone or EP combined with both drugs did not increase survival. Multivariate analysis showed that the pre-radiotherapy status was an independent factor, and IMRT technology could reduce this survival effect. This study is a retrospective analysis. There may be a certain selection bias, no molecular typing analysis. We expect a large scale of domestic case registration and follow-up observation to obtain more comprehensive and reliable clinical data, so as to provide a more reliable basis for our clinical decision.