Clinical Characteristics,Treatment And Prognosis Of Primary Testis Diffuse Large B-cell Lymphoma

Research Background and PurposePrimary testicular lymphoma(PTL)is a rare testicular malignancy with low incidence,accounting for 3%-9%of testicular malignancies and 1%-2%.of Non-Hodgkin's lymphoma(NHL).The average age of onset is 66-68 years old.The first symptom is painless swelling of the unilateral or bilateral testes.The rare symptoms is abdominal pain and ascites caused by retroperitoneal lymph nodes.25%-40%patients with B symptoms.Pathological examination after orchiectomy is the gold standard for diagnosis,and 80%-90%of the pathological tissue type is diffuse large B cell lymphoma(DLBCL).Factors affecting prognosis include age,physical status score,B symptoms,extranodal lesions>1,large masses,and disease stage III/IV.Complete remission(CR)can be achieved after treatment,but some patients will still relapse several years after treatment.The recurrence of the contralateral testis or central nervous system(CNS)is a problem that needs special attention during treatment.In recent years,with the related research,its treatment plan has become more standardized but not yet fully unified.Clinically,comprehensive treatment options such as surgical resection,radiotherapy,chemotherapy and targeted therapy are mainly adopted.In this study,we collected the clinical data of 36 patients with primary testicular diffuse large B-cell lymphoma in our center and retrospectively analyzed its clinical features,evaluated the therapeutic effects of chemotherapy combined with intrathecal injection and radiation therapy and analyzed the prognosis.Relevant factors provide clinical guidance for improving the efficacy and prognosis of primary testicular diffuse large B-cell lymphoma.Methods and Methods(1)This is a single-center retrospective clinical study.We collected 36 cases of the primary testicular diffuse large B-cell lymphoma in the First Affiliated Hospital of Zhengzhou University from January 2007 to July 2017.(2)Chemotherapy:36 patients underwent orchiectomy,one patient with stage I disease received radiotherapy alone after surgery,one patient without any treatment after surgical resection,34 patients received chemotherapy after surgery:eleven patients were given the CHOP regimen(cyclophosphamide+epirubicin+vincristine+prednisone)regimen;two patients received CVP(cyclophosphamide+vincristine+prednisone);ten patients were given RCHOP(rituximab+cyclophosphamide+epirubicin+vincristine+prednisone);four patients discontinued rituximab for economic reasons and switched to CHOP after 4 cycles of RCHOP chemotherapy;three patients received 4 cycles of RCHOP and changed to mild cardiotoxicity to RCVP(rituximab+cyclophosphamide+vincristine+prednisone)chemotherapy;three patients did not have gain complete remission after 6 cycles of RCHOP converted to GDP(gemcitabine+cisplatin+dexamethasone)chemotherapy;one patient with stable after 4 cycle of RCHOP disease and changed to RGDP treatment.(3)Intrathecal injection and radiotherapy:32 of 36 patients received 4-8 cycle of CNS intrathecal injections(methotrexate 12 mg,cytarabine 50 mg,dexamethasone 5mg,21 days per cycle,intrathecal injection during chemotherapy).Eighteen patients underwent prophylactic contralateral testicular and/or lymph node irradiation.(4)Statistical methods:Statistical analysis was performed by Kaplan-Meier method,and the difference between survival curves was compared by Log-rank test.When P<0.05(two-sided test),it was statistically significant.Variable Cox proportional hazard regression was used for the analysis of prognostic factors.SPSS22.0 statistical analysis software(SPSS Inc.,Chicago,IL,USA)and GraphPad Prism5 statistical software were used.Results(1)The objective response rate(ORR)of 36 patients was 86.1%,23(63.9%)patients achieved CR,eight(22.2%)patients had partial response(PR).one(2.8%)patients with stable disease(SD),four(11.1%)patients in the initial efficacy evaluation progression disease(PD).(2)The median follow-up time of 36 patients was 40(4 to 101)months.The1-year,3-year,and 5-year OS rates were 100.0%,80.2%,and 72.9%,respectively.The 1-year,3-year,and 5-year PFS rates were 94.3%,68.0%,and 64.0%,respectively.There was a statistically significant difference in PFS between chemotherapy with rituximab and chemotherapy without rituximab(?~2=6.655,P=0.009),but no survival benefit on OS(?~2=2.903,P=0.088).The comprehensive treatment regimen of postoperative chemotherapy combined with intrathecal and radiotherapy had survival benefit in OS(?~2=14.040,P=0.004)and PFS(?~2=12.010,P=0.002).(3)Until to the follow-up time,ten patients had recurrence or progression,and the recurrence site included two contralateral testes,all of which were not receiving radiotherapy,followed by five cases of central nervous system,one case of lymph nodes,and two other extranodal organs.Eight patients died,five of whom died after recurrence,one patient had heart failure at 27 months of follow-up,one patient had cerebral hemorrhage at 10 months of follow-up,and one patient died of unexplained death at 26 months.(4)In the univariate survival analysis,age?70 years,stage III/IV,IPI score 3-5points,elevated?2-microglobulin were the survival factors of patients with primary testicular diffuse large B-cell lymphoma,the value were statistically significant(P<0.05).Multivariate prognostic analysis showed that stage III/IV,IPI score 3-5points were independent risk factors affecting the survival of patients with primary testicular diffuse large B-cell lymphoma.(5)Nine patients(25.0%)had grade III-IV hematologic toxicity,five patients(13.9%)with neutropenia,three patients(8.3%)with thrombocytopenia,and one patient(2.8%)with severe anemia.Eleven patients(30.6%)had grade III-IV non-hematologic toxicity,including one(2.8%)case hepatotoxicity,one case(2.8%)of cardiotoxicity,four cases(11.1%)of neurotoxicity,and three(8.3%)digestive tract reactions.Two patients(5.6%)discontinued chemotherapy after 4 cycles of chemotherapy.Most patients had no special symptoms after intrathecal injection,and some patients had slight dizziness.Conclusion(1)Statistical analysis of clinical data shows that chemotherapy combined with CNS prophylactic intrathecal and radiotherapy can improve the overall survival of patients with primary testicular diffuse large B-cell lymphoma;(2)patients receiving rituximab can delay recurrence,but no significant benefit in overall survival;(3)Stage III/IV,IPI score 3-5 points are independent risk factor affecting the survival of patients with primary testicular diffuse large B-cell lymphoma,suggesting a poor prognosis;(4)The adverse reactions during the chemotherapy process can be controlled without the occurrence of fatal adverse reactions.