Assosiation Between Bone Marrow Dose-volumetric Parameters And Acute Hematologic Toxicity In Anal Cancer Patients With Concurrent Chemoradiotherapy

Objective:In order to research the acute hematologic toxicity and identify clinical and dose-volumetric factors associated with hematologic toxicity during chemoradiotherapy for rectal cancer.Method:We analyzed 50 rectal cancer patients with concurrent chemotherapy and IMRT from January 2010 to March 2016 at oncology department of the Third Hospital of Hebei Medical University.There were 31 males and 19 females,respectively.The median age was 61 years and the mean age was 59.1 years(rang from 21 years to 76 years).Of all,19 patients have not been operated and 31 have been operated because of rectal cancer.There were 2 patients at phase I,24 at phase Ⅱ,17 at phase Ⅲ and 7 at phaseⅣ.Pathological type was adenocarcinoma.All patients were immobolized by thermoplastic elastomer and underwent CT simulation.GTV,CTV,PTV and organs of risk were drew according to the CT images,then were transmitted to CMS Xio 4.4 planning systems.The prescription dose of 95% PTV was45 Gy ~ 62Gy(median dose 48Gy).Radiation was delivered at 1.8 ~ 2.0Gy daily and 5 times per week.All patients were received concurrent Capecitabine1650mg/(m2d)bid 5 days per week.Patients were monitored routine blood test weekly during treatment.Acute hematologic toxicity was scored according to RTOG acute radiation injury classification standard.Some measures would be took to raise blood cell count if needed.The external contour of the PBM was delineated on the planning CT using bone windows.The PBM was devided into three subsites:iliac BM(IBM),lower pelvic BM(LPBM)and lumbosacral BM(LSBM).The pelvic dose-volume parameters included V10,V15,V20,V25,V30,V35,V40,average dose and volume of IBM,LPBM,LSBM and PBM.SPSS21.0 software package was used forstatistical analysis.Clinical factors were analyzed with χ2 test or Fisher’s exact,dosimetric factors were analyzed with t test or mann-whitney U test.Logistic regression models were used for multivariate analysis to test independent impact factors(P < 0.05).ROC curve was applied to evaluate dose-volume parameters which asossiated acute hematologic toxicity.Stepwise regression analysis was used to test the correlations between dose-volume parameters and HT endpoints.Result:1 In the follow-up period,there were 37 patients experienced acute hematologic toxicity,the overall incidence was 74.0%.Of which,46.0%(23),20.0%(10),8.0%(4),0(0)experienced Grade 1 to 4 acute hematologic toxicity,respectively.58.0%(29/50)paitents experienced acute leukopenia,24.0%(12/50)experienced acute neutropenia,24.0%(12/50)experienced acute anemia,and 8.0%(4/50)experienced acute thrombocytopenia.The median blood count nadir of WBC,NAC,Hgb,platelet during treatment were 3.73×109/L(range,1.89 ~ 8.07×109/L),2.34×109/L(range,0.8~ 6.8×109/L),117g/L(range,60.3 ~ 154.5g/L),163.5×109/L(range,57~268×109/L),respectively.2 The clinical factors of patients(gender,age,body mass index,clinical stage,have underwent surgery or not)were not associated with grade 2 or more acute hematologic toxicity(P>0.05).3 On univatiate analysis,IBM-V20,IBM-V25,IBM-35,IBM mean dose,LPBM-V20,LPBM-V25,LPBM-V30,LSBM-V15,PBM-V15,PBM-V20 and PTV volume were significantly associated with grade 2 or more acute leucopenia,PBM-V20 was significantly associated with grade 2 or more acute neutropenia.On multiple regression analysis,IBM-V20 and LSBM-V15 were independent impact factors of grade 2 or more acute leukopenia.The AUC(area under curve)of IBM-V20 and LSBM-V15 were 0.759 and0.709,respectively,the predictive value were 61.09% and 85.29%,specificity were 0.91 and 1,sensitivity were 0.67 and 0.49,respectively.The AUC(area under curve)of PBM-V20 was 0.81,the predictive value was83.59%,specificity and sensitivity were 0.96 and 0.75,respectively.On stepwise regression analysis,IBM-V10 was associated with WBC nadirs,standardized regression coefficient was-0.524(P < 0.001),LSBM-V10 was associated with ANC nadirs,standardized regression coefficient was-0.473(P=0.001),LSBM-V25 was associated with Hgb nadirs,standardized regression coefficient was-0.865(P=0.006).Conclusion:During concurrent chemoradiotherapy in anal cancer patients,the majority of occurrence of acute hematologic toxicity was Grade 1 to Grade 2.There was no relationship between clinical factors of patients and Grade 2 or more acute hematologic toxicity in this study.Increased low-dose radiation to PBM is associated with acute hematologic toxicity.IBM-V20、LSBM-V15 and、PBM-V20 were independent risk factors of grade 2 or more acute hematologic toxicity.