图像引导鼻咽癌调强放疗位置误差导致剂量差异分析

目的 分析千伏特锥形束CT(CBCT)对鼻咽癌调强放疗靶区中心位置变化及由位置偏差导致的剂量变化.方法 对21例鼻咽癌患者调强放疗,全程376次CBCT得到每次靶区中心变化值.在上述变化值中随机抽取10、15次值输入逆向调强放疗计划系统中,照射角度、子野序列、权重等均不变,只对中心发生变化;累积10、15次偏差计划得到新的剂量分布,通过偏差公式得到相对应次数标准计划剂量偏差情况.结果 未经校正的376次CBCT在左右、上下、前后方向的系统误差和随机误差分别为0.75 mm和1.13 mm,0.92 mm和2.15 mm,0.82 mm和1.24 mm,利用双参数模型计算CTV外扩4、6,4 mm生成PTV,左右、上下、前后方向＜2 mm的偏差比例分别为82.8%、76.0%、81.8%,＞3 mm偏差分别为6.2%、9.8%、7.1%.在15次累积计划时靶区接受95%处方剂量(D95)偏差为-7.5%～-11.9%,D50的为-5.1%～-8.2%.结论 每次较小的摆位误差可能对靶区或正常器官的剂量影响较小,但整个疗程累计30余次的误差结果可能导致较大剂量差异,通过双参数模型计算生成PTV并按PTV实现的计划和图像引导放疗可弥补这些剂量的不足.

Abstract：

Objective To discuss the set-up isocenter error based on kilovolt cone beam computed tomography (KVCBCT) and to investigate dose deviation led to set-up isocenter error. Methods 21 cases of nasopharyngeal carcinoma ( NPC ) treated with image guided intensity modulated radiotherapy (IG-IMRT)were investigated. The online KVCBCT scan, rigid image registration, set-up error was gained for 376 sets before radiotherapy. We sampled ten and fifteen setup isocenter error in the 376 sets randomly. Without changing beam angle,fields size and leaf sequences and dose weight et al. , we only replaced new isocenter and accumulated the new plan for ten or fifteen plans. We compared the percentage deviation between ten,fifteen times accumulated plans and normal ten , fifteen times plans. Results All 376 sets of KVCBCT image were analyzed for 21 cases. Under the condition of non-correction, the setup isocenter errors are 0. 75mm ± 1.13 mm, 0. 92 mm ±2. 15 mm,0. 82 mm ± 1.24 mm in left-right, superior-inferior and anteriorposterior directions respectively. So, we developed the margins which were 4 mm,6 mm、4 mm in three directions respectively from clinical tumor volume to planning tumor volume (PTV) calculated by two parameters model. In the fifteen accumulated plan, the deviation in the dose of 95% PTV (D95) was -7. 5% - - 11.9%, and the deviation in the D50 was -5. 1% - -8. 2%. Conclusions It is possible of small effects to normal organs and targets because of small error of patient displacement in one fraction.However, many small errors can led to considerable dose difference in targets and normal tissue in thirty fractions of all treatments period. So, according to two parameters model, PTV margin can be designed new planning and depended on IG-IMRT technique, which it will be significantly reduced these dose differences.     

基于头颈部千伏级锥形束CT的剂量计算研究

目的 探讨用机载千伏级锥形束CT (CBCT)对鼻咽癌患者治疗前扫描图像直接进行剂量计算的可行性.方法 选取治疗前行扇形束CT (FBCT)和CBCT扫描的11例鼻咽癌患者,将体位校正后重新扫描的CBCT图像传输至治疗计划系统中.在治疗计划系统中将FBCT和CBCT图像融合,将FBCT的计划移植至CBCT上.选择CBCT图像自己的HU-ED校正曲线重新进行剂量计算,与FBCT计划的靶区和正常器官的剂量体积直方图以及等中心层面剂量分布的γ通过率分析(阈值3%/3 mm)结果进行比较.结果 11例鼻咽癌患者中CBCT和FBCT计划的剂量体积直方图相似,等中心层面剂量分布中平均γ通过率为98.0%±1.33%.FBCT计划和CBCT计划的靶区受量差异都<1%,正常组织器官受量差异<2%.结论 治疗过程中得到的CBCT图像能用来进行剂量计算.

Abstract：

Objective To study the feasibility of dose calculation using kilovoltage X-ray cone-beam CT (KVCBCT) imaging for head-and-neck radiation therapy.Methods 11 patients with nasopharyngeal carcinoma were scanned with KVCBCT to adjust position before treatment, and rescanning images with KVCBCT after correction were input a treatment-planning system.The dose was recalculated by applying the patients′ treatment plans based on planning CT to the KVCBCT images.The dose distributions and dose volume histograms (DVH) of the tumor and critical structures were compared with the original treatment plan.Results The DVH and dose distribution of the plan based on the KVCBCT are compared with that of the planning CT, and they shows a good consistency for the 11 cases.The doses calculated from the planning CT and KVCBCT were compared on the isocenter planes.Using γ analysis with a criterion of 3%/3 mm, 98.0%±1.33% of the points on the isocenter planes in the planning CT and KVCBCT.The difference of the dose to target volume was<1% and to normal structure was<2%.Conclusions This study indicated that CBCT images can be used to make a treatment plan with its individual hounsfield unit-electron density calibration curve.     

应用锥形束CT对盆腔肿瘤放疗计划靶区外放距离的研究

Objective To analyze setup errors for irradiation of pelvic carcinoma by online conebeam CT (CBCT) scanning and to calculate the external margins from clinical target volume (CTV) to planning target volume (PTV) in treatment planning. Methods Twelve patients with rectal or prostate cancer were enrolled in this study. Translational errors (x,y,z) and rotational errors (u,v,w) were obtained by using CBCT in radiotherapy. Results The set-up errors were gathered from 229 sets of CBCT in 12patients. The systemic ± random errors on x,y,z, u,v and w axes were (0.49 ± 1.18) mm, (-0. 11 ±3.45) mm, (-2. 00 ± 1.59) mm, 1.14°±0. 67°, 0. 42°±O. 94°and -0. 32°±±0. 68°, respectively. Setup errors in the left-right, anterior-posterior, and superior-inferior directions were 4. 6 mm, 12. 5 mm, and 6. 2 mm, respectively. Conclusions Set-up errors were unavoidable in pelvic carcinoma irradiation. To minimize the influence of set-up errors, we suggest a PTV margin of 5 mm, 15 mm and 10 mm in the leftright, anterior-posterior and superior-inferior directions, respectively.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

Feasibility of the partial-single arc technique in RapidArc planning for prostate cancer treatment

The volumetric modulated arc therapy(VMAT)technique,in the form of RapidArc,is widely used to treat prostate cancer.The full-single arc(f-SA)technique in RapidArc planning for prostate cancer treatment provides efficient treatment,but it also delivers a higher radiation dose to the rectum.This study aimed to compare the dosimetric results from the new partial-single arc(p-SA)technique with those from the f-SA technique in RapidArc planning for prostate cancer treatment.In this study,10 patients with lowrisk prostate cancer were selected.For each patient,two sets of RapidArc plans(f-SA and p-SA)were created in the Eclipse treatment planning system.The f-SA plan was created using one full arc,and the p-SA plan was created using planning parameters identical to those of the f-SA plan but with anterior and posterior avoidance sectors.Various dosimetric parameters of the f-SA and p-SA plans were evaluated and compared for the same target coverage and identical plan optimization parameters.The f-SA and p-SA plans showed an average difference of±1%for the doses to the planning target volume(PTV),and there were no clear differences in dose homogeneity or plan conformity.In comparison to the f-SA technique,the p-SA technique reduced the doses to the rectum by approximately 6.1%to 21.2%,to the bladder by approximately 10.3%to 29.5%,and to the penile bulb by approximately 2.2%.In contrast,the dose to the femoral heads,the integral dose,and the number of monitor units were higher in the p-SA plans by approximately 34.4%,7.7%,and 9.2%,respectively.In conclusion,it is feasible to use the p-SA technique for RapidArc planning for prostate cancer treatment.For the same PTV coverage and identical plan optimization parameters,the p-SA technique is better in sparing the rectum and bladder without compromising plan conformity or target homogeneity when compared to the f-SA technique.     

应用锥形束CT对盆腔肿瘤放疗计划靶区外放距离的研究

Objective To analyze setup errors for irradiation of pelvic carcinoma by online conebeam CT (CBCT) scanning and to calculate the external margins from clinical target volume (CTV) to planning target volume (PTV) in treatment planning. Methods Twelve patients with rectal or prostate cancer were enrolled in this study. Translational errors (x,y,z) and rotational errors (u,v,w) were obtained by using CBCT in radiotherapy. Results The set-up errors were gathered from 229 sets of CBCT in 12patients. The systemic ± random errors on x,y,z, u,v and w axes were (0.49 ± 1.18) mm, (-0. 11 ±3.45) mm, (-2. 00 ± 1.59) mm, 1.14°±0. 67°, 0. 42°±O. 94°and -0. 32°±±0. 68°, respectively. Setup errors in the left-right, anterior-posterior, and superior-inferior directions were 4. 6 mm, 12. 5 mm, and 6. 2 mm, respectively. Conclusions Set-up errors were unavoidable in pelvic carcinoma irradiation. To minimize the influence of set-up errors, we suggest a PTV margin of 5 mm, 15 mm and 10 mm in the leftright, anterior-posterior and superior-inferior directions, respectively.     

颈段食管癌质子治疗与调强放疗计划对比研究

目的 比较质子治疗(PT)与X线调强放疗(IMRT)在颈段食管癌治疗中的剂量分布.方法 选取10例颈段食管癌患者CT图像,每例制定1个X线IMRT计划(7个野)与2个PT计划(PT1为前后对穿2个野,PT2为两前斜加后3个野).使用等剂量分布及剂量体积直方图进行计划间比较.结果 IMRT与PT1、PT2计划的计划靶体积(PTV)95%等剂量面适形指数分别为1.43与1.52、1.43(F=3.62,P<0.01),平均剂量分别为64.4 Gy与65.0、63.6 Gy(F=12.06,P<0.01);PTV周围正常组织平均剂量分别为20.7 Gy与10.5、10.6 Gy(F=77.60,P<0.01),全肺的为12.1 Gy与7.3、8.4 Gy(F:15.87,P<0.01),脊髓最大剂量分别为41.4 Gy与34.9、35.0 Gy(F=11.74,P<0.01).结论 3个计划均能满足覆盖靶区要求,但PT可明显降低肿瘤周围正常组织剂量,这为PT剂量提升或合并使用同期化疗提供了可能.PT计划中前后对穿2个野也可满足临床要求.

Abstract：

Objective To compare the dosimetric difference of proton therapy(PT)and X-ray intensity-modulated radiotherapy(IMRT)for cervical esophageal cancer.Methods The treatment planning of 10 patients with cervical esophageal cancer were selected for this study.One IMRT plan and 2 PT plans (PT1 plan:two opposed AP-PA beams;PT2 plan:two anterior-oblique beams and one posterior beam)were constructed for each patient.The isodose distribution and statistical data extracted from dose volume histograms were used for dose plan comparison.Results The conformal index(CI95%,defined as the ratio between the volume receiving at least 95%of the prescribed dose and the volume of PTV)of IMRT,PT1 and PT2 was 1.43,1.52 and 1.43(F=3.62,P<0.01),respectively.And the mean dose of PTV was 64.4 Gy,65.0 Gy and 63.6 Gy(F=12.06,P<0.01);the mean dose in normal tissue outside of PTV was 20.7 Gy,10.5 Gy and 10.6 Gy(F=77.60,P<0.01),in whole lung was 12.1 Gy,7.3 Gy and 8.4 Gy (F=15.87,P<0.01);the maximum dose in spinal cord was 41.4 Gy,34.9 Gy and 35.0 Gy(F=11.74,P<0.01),respectively.Conclusions Ail plans full file the requirements for PTV,however.PT plans can reduce radiation dose in surrounding normal significantly.The possibility is provided to escalate PT dose in PTV or to combine more aggressive chemotherapy.The PT1 plan full fills the clinical requirements.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Résumé: Lefficacité optimale des fluoropyrimidines nécessite des concentrations élevées en 5-10 méthylènetétrahydrofolate (CH₂FH₄), contrôlées par la méthylènetétrahydrofolate réductase (MTHFR) qui convertit irréversiblement le CH₂FH₄ en 5-méthyltétrahydrofolate (CH₃FH₄). Les polymorphismes 677CT et 1298AC du gène MTHFR sont associés à une baisse dactivité de lenzyme. Les tumeurs «MTHFR mutées» devraient donc être plus sensibles aux fluoropyrimidines que les tumeurs «MTHFR sauvages». Les études expérimentales et cliniques publiées à ce jour tendent à montrer une plus grande sensibilité au 5-FU (associé ou non à lacide folinique) dans les tumeurs MTHFR mutées par rapport aux tumeurs sauvages. Ces résultats montrent la nécessité de poursuivre ces recherches afin de confirmer limpact de ces polymorphismes sur lefficacité des fluoropyrimidines.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

PSA-Test zur Früherkennung des Prostatakarzinoms

Zusammenfassung Prostatakrebs ist hierzulande seit einigen Jahren die häufigste Krebserkrankung bei Männern. Da über die Ätiologie wenig gesichertes Wissen vorliegt und daher kaum Möglichkeiten zur primären Prävention bestehen, konzentrieren sich die Anstrengungen auf die Suche nach wirksamen Verfahren zur sekundären Prävention. Hierbei gilt die Verwendung des PSA-Tests zur Früherkennung des Prostatakarzinoms als derzeit aussichtsreichstes Verfahren. Bevor ein neues Früherkennungsverfahren zur breiten Anwendung empfohlen oder in das gesetzliche Früherkennungsprogramm aufgenommen wird, muss jedoch seine Wirksamkeit in hierfür geeigneten wissenschaftlichen Untersuchungen nachgewiesen werden. Bis jetzt gibt es bereits eine ganze Reihe epidemiologischer Studien zur Effektivität des PSA-Screenings, doch konnte ein Wirksamkeitsnachweis bisher nicht erbracht werden. Zwei große randomisierte Studien in Europa und den USA lassen für die Jahre 2005–08 erste Ergebnisse erwarten. Da epidemiologische Arbeiten belegen, dass durch PSA-Screening eine nicht unerhebliche Überdiagnostik und Übertherapie eintritt, d. h. Schaden angerichtet werden kann, ist das Ergebnis der genannten randomisierten Studien vor weitergehenden Entscheidungen unbedingt abzuwarten. Bis dahin sollte von der Anwendung des PSA-Tests zur Prostatakrebsfrüherkennung unmissverständlich abgeraten werden. Da für den Test bereits ausgiebig Werbung betrieben wurde, kommt einer gründlichen ärztlichen Aufklärung von an dem Test interessierten Personen eine Schlüsselrolle zu.     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

异基因造血干细胞移植后患者肝损害病因与临床特征分析

 【摘要】　目的　总结异基因造血干细胞移植（allo-HSCT）后患者肝损害的发生率、发生原因、诊断方法与治疗选择。方法　回顾性分析郑州大学附属肿瘤医院2006～2010年接受allo-HSCT的83例良、恶性血液病患者中Ⅱ～Ⅳ级肝损害的发生率、各种病因的构成比、临床表现以及诊断方法,分析移植后不同时期肝损害病因的差异、治疗方法、疗效。结果　83例allo-HSCT患者中,发生Ⅱ～Ⅳ级肝损害45例（54.2 %）。按肝损害致病病因分类,预处理化疗所致7例,环孢素所致9例,肝静脉闭塞病（HVOD）所致2例,肝脏移植物抗宿主病（GVHD）所致24例,乙型肝炎病毒再激活所致2例,多器官衰竭所致1例。发生于移植后1个月内者20例（44.4 %）,以药物性肝损害为主,1个月～100 d者13例（28.9 %）,101 d～1年者12例（26.7 %）,均以肝脏GVHD为主。经减停肝损害药物、抗排异、保肝等治疗后,27例治愈,10例好转,2例未愈,6例死于原发病复发或移植相关并发症。结论　肝损害是allo-HSCT后常见的并发症,药物及肝脏GVHD是其最主要的致病原因,肝损害与其发生时间的相关性可作为肝损害病因学诊断的参考依据。根据肝损害的病因选择针对性的治疗方法,可取得较好的疗效。     

Pharmacokinetics and dosage of fluconazole in continuous hemofiltration (CAVH, CVVH) and hemodialysis (CAVHD, CVVHD)

Continuous haemofiltration (CAVH, CVVH) and haemodialysis (CAVHD, CVVHD) are increasingly used in patients with acute renal failure (ARF). The elimination rates of fluconazole vary considerably among the different procedures. In CVVHD, the elimination rate is, depending on the combined dialysate/ultrafiltrate flow rate, the most marked compared to CVVH and intermittent dialysis with a fluconazole clearance exceeding the values of healthy persons in CVVHD 2 L/h. To achieve therapeutic plasma levels during continuous renal replacement therapy, the same loading dose as in patients without renal failure should be applied, followed by the adjusted maintenance dose for anuric patients multiplied by a factor taking the extracorporeal elimination of the absorbed dose into account (CAVH, CVVH: x 2.2, ultrafiltrate flow 0.5 L/h; CAVHD, CVVHD: x 3.8, combined dialysate/ultrafiltrate flow 1.5 L/h). Despite the broad therapeutic margin of fluconazole, drug monitoring is recommended with respect to the very limited number of investigations with relatively low dosages up to 200 mg/day and--which is of paramount importance--to achieve therapeutic drug levels in vital indications.