| Part ? Analysis on Risk Factors of Platinum-based Ototoxicity in Patients with Neuroblastoma and HepatoblastomaObjectives: To investigate the condition of audiological evaluation and hearing damage in Neuroblastoma(NB)or Hepatoblastoma(HB)patients with platinum-based chemotherapy;to explore the risk factors inducing platinum-induced ototoxicity.Methods: The clinical data of 360 NB or HB patients treated at Xinhua Hospital during January 2005 to September 2015 were collected,including gender,age at exposure to platinum,accumulated platinum dosage(mg/m2),and results of hearing tests.This study analysed the incidence and risk factors of platinum-induced ototoxicity in patients with solid tumor.Results:1.Analysis on clinical data: The inclusion criteria include receiving more than 2 courses with platinum drugs and accepting audiological tests in our hospital.From February 2005 to Septmber 2015,a total of 360 patients diagnosed with NB or HB received platinum-based chemotherapy in our hospital,and 28 NB and 13 HB patients were accorded with the inclusion criteria.The male/female ratio was 3.3:1,and the median age of treatment was 2.2 years old.Among 41 patients in our study,the cumulative dosage of cisplatin was 692.7±336.3 mg/m2,carboplatin was 1550±725mg/m2.Eight patients received the combined therapy of cisplatin and carboplatin,and none of them have suffered from hearing loss.Out of 33 patients received cisplatin-based chemotherapy,11 patients showed up significant hearing damage(Chang grading?2a).2.Risk factors of ototoxicity: The risk-predicting model suggested that cumulative cisplatin dosage was independently risk factor of cisplatin-induced ototoxicity.The results of univariate analysis indicated that There was significant difference in the risk of hearing loss between patients younger than 3 years and older than 3 years old(P=0.031);and patients receiving accumulated cisplatin dosage ? 400mg/m2 were more likely to suffer from ototoxicity,than<400mg/m2(P=0.003).Further using logistic-regression analysis,the Wald test showed that cumulative cisplatin dosage ?400mg/m2 was an independently significant predictor for hearing impairment for NB and HB patients(P=0.014,95% CI=1.001–1.007),however younger than 3 years was not an independent factor on platinum-based ototoxicity.Conclusioins:1.Accumulative cisplatin dosage ? 400mg/m2 was an independently significant predictor for hearing impairment in NB and HB patients(P=0.014,95% CI=1.001–1.007).2.Patients receiving combined treatment of cisplatin and carboplatin have not showed up hearing loss,indicating that ototoxicity induced by cisplatin was more serious than carboplatin.Patients reciving platinum drugs should accept audiological tests regularly.3.Youger than 3 years of age at treatment has been reported one of independent risk factors,however the result has not indicated that it was an independent influence on platinum-based ototoxicity in this study.And this could be related to small sample.Part ? Analysis on the Relationship Between the Prognosis and Expression Level of ?-catenin?Gli1 Protein in Hepatoblastoma PatientsObjects: To research the relationship and correlation among the expression level of ?-catenin?Gli1 protein,the clinical characteristics,and the prognosis of hepatoblastoma(HB)patients.Methods: The clinical data of 34 HB patients treated at Xinhua Hospital were retrospectively analysed(including gender,age at diagnosis,dynamic change of alpha fetoprotein characteristics,histopathological types,chemotherapeutic regiments,time to disease progression or relapse,and survival state),and paraffin-embedded tumor specimens of biopsy or surgery were collected.The expression levels of ?-catenin and Gli1 protein were tested by method of immunohistochemistry,then the correlation between the expression levels of ?-catenin?Gli1 protein and the prognosis in HB patients was analysed.Results:1.Analysis on clinical data: The male/female ratio of 34 HB patients was2.4:1,the median age was 12.5 months,and the median follow-up time was 50 months.The histopathological type of 21 patients was embryonal HB,13 was fetal HB,and 6 experienced metastasis at diagnosis.According the pretreatment extent of disease(PRETEXT)staging,there were 2patients of stage ?,8 of stage ?,20 of stage ?,4 of stage ?;sorted by the postoperative stage of children's oncology group(COG),82.4%(28/34)patients were stage ?,17.6%(6/34)were stage ?.The 4 year overall survival of the 34 patients was 77±8%,the 4 year event-free survival rate was 71±8%.There were 8 patients died up to the follow-up deadline,3survivals with disease and 23 patients obtaining event-free survival.2.Results of immunohistochemistry test: Among 34 patients,the nuclear?-catenin staining were(-)?(+)?(++)in tumor specimens from 8?13?13 HB patients respectively,and the positive rate was 76.5%.The sorces for the nuclear Gli1 staining were(-)?(+)in tumor specimens from 29?5HB patients respectively,and the positive rate was 14.7%.Applying Spearman correlation analysis,the results indicated that the nuclear?-catenin and Gli1 staining existed negative relationship(P=0.007).3.Survival analysis: This study analyzed the correlation between the prognosis and factos(gender,age at diagnosis,expression level of?-catenin ? Gli1 protein,histopathological types,tumor stages and dynamic change of alpha fetoprotein).The results indicated that nuclear?-catenin expression in different histopathological types existed significant discrepancy.The epression levels of nuclear ?-catenin in embryonal type were higher than fetal type(P=0.016).The results of univariate Cox regression analysis suggested a statistically significant correlation between epression levels of nuclear ?-catenin and event-free survival(P=0.037,95%CI=1.031-2.588).The COG staging was statistically relevant to disease-free survival,and patients with higher stage have greater risk to progress or replase(P=0.041,95%CI=0.078-0.951).There was significant correlation between the decline in AFP after the first cycle of chemotherapy and event-free survival(P=0.024,95%CI=0.071-0.831).The results of multivariate Cox regression analysis indicated that nuclear?-catenin epression and decline in AFP after the first cycle of chemotherapy were independent influences of event-free survival.Increase in nuclear ?-catenin epression resulted in greater risk of progression ?relapse or death(P=0.013,95%CI=1.246-6.556).And patients with decline of < 1 log in AFP after the first cycle of therapy had higher risk of progression?relapse or death than patients with decline of ?1 log in AFP(P=0.009,95%CI=0.019-0.570).Conclusions:1.The nuclear expression of ?-catenin and Gli1 protein existed negative relationship(P=0.007).2.The nuclear ?-catenin expression in different histopathological types existed significant discrepancy.The nuclear epression of ?-catenin in embryonal type was higher than fetal type(P=0.016).3.The results of Cox regression analysis indicated that the nuclear epression level of ?-catenin was an independent influence of event-free survival.Increase in nuclear ?-catenin expression resulted in greater risk of progression?relapse or death(P=0.013,95%CI=1.246-6.556).4.Patients with decline of < 1 log in AFP after the first cycle of chemotherapy had higher risk of progression?relapse or death than patients with decline of ?1 log in AFP(P=0.009,95%CI=0.019-0.570). |
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