KRAS mutations are not predictive for progression of preneoplastic gastric lesions.

Individuals with atrophic gastritis (n = 863) were recruited to participate in a chemoprevention trial in Nari?o, Columbia. The volunteers were randomly assigned to intervention therapies, which included antibiotic treatment for Helicobacter pylori infection, and then daily dietary supplementation with antioxidant micronutrients in a 2(3) factorial design. Biopsies were obtained according to a specified protocol from designated areas in the stomach for each individual at baseline (before intervention therapy), at year 3, and at year 6. A systematic sample of 160 participants was selected from each of the eight treatment combinations, and the first exon of KRAS was examined for mutations. At year 3, the data indicated that individuals with KRAS mutations in their baseline premalignant stomach biopsies were 3.74 times as likely to progress to a higher premalignant stage than those who lacked baseline mutations (P = 0.04; C. Gong et al., Cancer Epidemiol. Biomark. Prevy. 8:167-171, 1999). However, after 6 years, baseline KRAS mutations failed to predict histological progression. Also, KRAS mutation in 72-month biopsies did not predict histological progression.     

Rectal dose reduction with IMRT for prostate radiotherapy

Dose escalation in radiation therapy has led to increased control rates with some clinical trial evidence that rectal toxicity may be reduced when using intensity-modulated radiotherapy (IMRT) over 3D conformal radiotherapy (3DCRT) for dose-escalated prostate radiotherapy. However, IMRT for prostate patients is not yet standard in many Australian radiation oncology centres. This study investigates dosimetric changes that can be observed between IMRT and 3DCRT in prostate radiotherapy. Fifteen patients were selected for analysis. Two target definitions were investigated – prostate-only and prostate plus seminal vesicles (p + SVs). A five-field 3DCRT and seven-field IMRT plan were created for each patient and target definition. The planning target volume coverage was matched for both plans. Doses to the rectum, bladder and femoral heads were compared using dose volume histograms. The rectal normal tissue complication probabilities (NTCPs) were calculated and compared for the 3DCRT and IMRT plans. The delivery efficiency was investigated. The IMRT plans resulted in reductions in the V25, V50, V60, V70 and V75 Gy values for both the prostate-only and p + SVs targets. Rectal NTCP was reduced with IMRT for three different sets of model parameters. The reductions in rectal dose and NTCP were much larger for the p + SVs target. Delivery of IMRT plans was less efficient than for 3DCRT plans. IMRT resulted in superior plans based on dosimetric and biological endpoints. The dosimetric gains with IMRT were greater for the more complex p + SVs target. The gains made came at the cost of decreased delivery efficiency.     

Steep dose gradients for simultaneous integrated boost IMRT

Steep dose gradients between two planning target volumes (PTVs) as may be required for simultaneous integrated boosts (SIB) should be an option provided by IMRT algorithms. The aim was to analyse the geometry of the SIB problem and to implement the results in an algorithm for IMRT segment generation denoted two-step intensity modulated radiotherapy (2-Step IMRT). It was hypothesized that a gap between segments directed to the inner and the outer PTV would steepen the dose gradient. The mathematical relationships were derived from the individual dose levels and the geometry (diameters) of the PTVs. The results generated by means of 2-Step IMRT segments were equivalent or better than the segment generation using a commercial IMRT planning system. The dose to both the inner and the outer PTV was clearly more homogeneous and the composite objective value was the lowest. The segment numbers were lower or equal – with better sparing of the surrounding tissue. In summary, it was demonstrated that 2-Step IMRT was able to achieve steep dose gradients for SIB constellations.     

Patient-specific point dose measurement for IMRT monitor unit verification

PURPOSE: To review intensity-modulated radiation therapy (IMRT) monitor unit verification in a phantom for 751 clinical cases. METHODS AND MATERIALS: A custom water-filled phantom was used to measure the integral dose with an ion chamber for patient-specific quality assurance. The Corvus IMRT planning system was used for all cases reviewed. The 751 clinical cases were classified into 9 treatment sites: central nervous system (27 cases), gastrointestinal (24 cases), genitourinary (447 cases), gynecologic (18 cases), head and neck (200 cases), hematology (12 cases), pediatric (3 cases), sarcoma (8 cases), and thoracic (12 cases). Between December 1998 and January 2002, 1591 measurements were made for these 751 IMRT quality assurance plans. RESULTS: The mean difference (MD) in percent between the measurements and the calculations was +0.37% (with the measurement being slightly higher). The standard deviation (SD) was 1.7%, and the range of error was from -4.5% to 9.5%. The MD and SD were +0.49% and 1.4% for MIMiC treatments delivered in 2-cm mode (261 cases) and -0.33% and 2.7% for those delivered in 1-cm mode (36 cases). Most treatments (420) were delivered using the step-and-shoot multileaf collimator with a 6-MV photon beam; the MD and SD were +0.31% and 1.8%, respectively. Among the 9 treatment sites, the prostate IMRT (in genitourinary site) was most consistent with the smallest SD (1.5%). There were 23 cases (3.1% of all cases) in which the measurement difference was greater than 3.5%; of those, 6 cases used the MIMiC in 1-cm mode, and 14 of the cases were from the head-and-neck treatment site. CONCLUSION: IMRT monitor unit calculations from the Corvus planning system agreed within 3.5% with the point-dose ion chamber measurement in 97% of 751 cases representing 9 different treatment sites. A good consistency was observed across sites.     

Cytokine concentrations are not predictive of bacteremia in febrile neutropenic patients

Assay of cytokines and C reactive protein (CRP) in different periods of febrile neutropenia may be helpful for early defining the risk in severe infections. We determined serum interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and CRP in 22 previously untreated patients with various malignancies. Samples were obtained in four different clinical periods of febrile neutropenia; prior to chemotherapy, afebrile neutropenic period after chemotherapy, febrile neutropenic period, and recovery period. When compared to sex-and age-matched group of healthy subjects, IL-6, IL-8, sIL-2R, and CRP levels were found to be elevated in all periods. The highest levels were encountered in the febrile neutropenic period. For predictivity purposes, the afebrile neutropenic period was the most important period. Serum sIL-2R, IL-6, IL-8 and CRP levels were elevated in this period. IL-8 levels showed the most stable elevation through different stages of febrile neutropenia. Serum IL-8 levels were found to have the most reliable and stable elevation in different clinical stages of febrile neutropenia. Nevertheless, IL-8 is not able to discriminate among risk groups and cannot be used as a predictive factor.     

RBE values for neutron therapy: A simple method for converting acceptable photon dose to limiting neutron dose

The general clinical use of an RBE of 3 for neutrons is shown to be not only incorrect but also dangerous. RBE is dependent on the dose/fraction of either photons or neutrons and differs for different tissues. It is particularly high for the CNS at the doses/fraction used in therapy. Data from neutron therapy trials are used to illustrate the dangers of using an RBE of 3 regardless of dose/fraction or tissue and to compare the estimated tolerance level for spinal cord with clinical findings. It is suggested that for clinical use RBE should normally be plotted against photon dose/fraction. Neutron tolerance can then be determined directly from the total dose in an acceptable photon schedule by using the RBE at the photon dose/fraction used in the photon schedule. No NSD relationship need then be assumed, thus reducing the uncertainties. The RBE for the CNS is contrasted with that for skin damage; at a photon dose/fraction of 180 rad, the RBE for the CNS is about 5.3, compared with about 4.3 for skin damage. The estimate of tolerance to the cervical cord is 850 rad neutrons. This is in good agreement with clinical findings.     

调强放射治疗剂量验证研究进展

 调强放射治疗（IMRT）以其较好的靶区剂量分布和保护正常组织等特点已在国内多家医疗单位开展。但是由于此项治疗技术受到诸如影像、逆向计划设计、精确定位及治疗设备等因素的影响，对于治疗方案的剂量验证显得尤为重要。现对近年来世界多个国家的肿瘤组织关于IMRT计划剂量验证方面的研究作一综述。     

Additional dose constraints for analytical beam weighting optimization in IMRT.

This work presents an improvement to an algorithm for analytical beam weighting optimization where a flexible objective function, which considers 'importance factors' for each anatomical region and 'allowed deviations' from the prescribed dose, is defined. This upgrading allows forcing the mean value of the dose distribution to be the desired value, by using Lagrange multipliers. A real case is presented to show the effect of this change.     

宫颈癌术后IMRT中骨盆受量评估及预测

目的 宫颈癌术后IMRT中通过分析两种骨盆的定义方法以及骨盆受量的影响因素来评估和预测骨盆的剂量,为宫颈癌术后IMRT中骨盆的保护提供参考。方法 选择60例骨盆未限量的宫颈癌术后IMRT患者,按照解剖方法和Mell方法勾画两种骨盆轮廓(骨盆解剖、骨盆Mell),基于骨盆解剖限量重新设计治疗计划后分析两者的剂量关系。应用Pearson法分析相关性,Logistic多元回归分析影响骨盆解剖剂量的因素并建立剂量预测模型。结果 骨盆解剖、骨盆Mell体积分别为925.82、1141.20cm³(P=0.000)。骨盆解剖与骨盆Mell剂量存在相关性(r>0.622,P=0.000),前者剂量明显大于后者;两者V10、V20、V30的关系分别为y=-8+1.01x、y=-13+1.05x、y=-4+0.9x。文献推荐骨盆Mell限量标准(V10≤90%、V20≤75%、V30≤60%)经计算得到相应骨盆解剖限量标准为V10≤97%、V20≤83%、V30≤70%。骨盆解剖限量后可降低受量,其中V10、V20、V30、Dmean分别降低3.64%、12.69%、12.02%、6.93%(P=0.000、0.000、0.000)。多因素分析显示骨盆解剖重叠在PTV内的相对体积是骨盆解剖剂量的影响因素(P<0.05),当重叠体积<18%时骨盆限量易达到剂量限值要求。结论 宫颈癌术后IMRT中两种骨盆定义方法均能应用于临床,骨盆限量能显著降低其剂量。骨盆重叠在PTV内的相对体积是骨盆剂量的独立影响因素,重叠体积小于18%的患者其骨盆限量后易达到剂量限值要求。     

宫颈癌术后IMRT中骨盆受量评估及预测

目的 宫颈癌术后IMRT中通过分析两种骨盆的定义方法以及骨盆受量的影响因素来评估和预测骨盆的剂量,为宫颈癌术后IMRT中骨盆的保护提供参考。方法 选择60例骨盆未限量的宫颈癌术后IMRT患者,按照解剖方法和Mell方法勾画两种骨盆轮廓(骨盆解剖、骨盆Mell),基于骨盆解剖限量重新设计治疗计划后分析两者的剂量关系。应用Pearson法分析相关性,Logistic多元回归分析影响骨盆解剖剂量的因素并建立剂量预测模型。结果 骨盆解剖、骨盆Mell体积分别为925.82、1141.20cm³(P=0.000)。骨盆解剖与骨盆Mell剂量存在相关性(r>0.622,P=0.000),前者剂量明显大于后者;两者V10、V20、V30的关系分别为y=-8+1.01x、y=-13+1.05x、y=-4+0.9x。文献推荐骨盆Mell限量标准(V10≤90%、V20≤75%、V30≤60%)经计算得到相应骨盆解剖限量标准为V10≤97%、V20≤83%、V30≤70%。骨盆解剖限量后可降低受量,其中V10、V20、V30、Dmean分别降低3.64%、12.69%、12.02%、6.93%(P=0.000、0.000、0.000)。多因素分析显示骨盆解剖重叠在PTV内的相对体积是骨盆解剖剂量的影响因素(P<0.05),当重叠体积<18%时骨盆限量易达到剂量限值要求。结论 宫颈癌术后IMRT中两种骨盆定义方法均能应用于临床,骨盆限量能显著降低其剂量。骨盆重叠在PTV内的相对体积是骨盆剂量的独立影响因素,重叠体积小于18%的患者其骨盆限量后易达到剂量限值要求。     

Expression of dose in neutron therapy

A pragmatic approach in neutron dosimetry is to consider the energy spectrum to consist of a neutron and a gamma component. The relationship between the two components of dose in neutron radiotherapy has been investigated for energies currently in clinical use. Changes in the neutron component itself are not dealt with. Because the two components are given simultaneously there is some interaction between them so that the gamma fraction is more effective than if the neutron and gamma doses were separated in time. This interaction has been accounted for using a well-proven extension of the linear-quadratic (LQ) equation. Using values of the LQ parameters alpha and beta measured recently in vivo, we have modelled the total effect from the neutron and gamma dose-contributions in terms of an equivalent neutron dose. This allows a comparison of different methods of expressing the measured physical dose with the biologically effective dose. The current practice in neutron therapy is to give the total (neutron plus gamma) dose, quoting also the gamma contamination. In all cases within the range of energies used for therapy, the total dose will give an overestimate of the biologically effective dose by approximately 4% for each 5% of gamma contamination. Expression of the neutron dose only (ignoring the gamma component) will give an underestimate of the biologically effective dose by approximately 1.5% for each 5% of gamma contamination, i.e. the error is approximately three times less for neutron dose than for total dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

EBT剂量胶片测量电子线百分深度剂量的应用研究

目的 研究EBT剂量胶片在临床电子线百分深度剂量(PDD)中的测量方法.方法 采用14.7 cm×5.1 cm的矩形射野,在同一张EBT胶片上进行5阶梯度的剂量刻度.应用上述刻度方法,针对4、6、8、10、12和15 MeV电子线,在小水箱中采用竖直和倾斜5°两种方式测量PDD,并与半导体探头的三维水箱扫描结果以及平行板电离室在小水箱中测量结果进行比较和分析°结果当剂量胶片上端与水面平齐时,EBT测量的PDD曲线与两种探头测量的结果具有较好一致性,并且倾斜和竖直测量两种方式无明显差异.当剂量胶片上端伸出水面时,在竖自测量方式下剂量建成区内测量结果明显低于其他测量结果,而倾斜测量方式下则无明显影响.结论 新的剂量刻度方式快捷可靠,可显著减少剂量胶片用量.在测量电子线PDD时建议将胶片倾斜一定角度进行,以便减小胶片上端与水面不平齐所引起的测量误差.     

EBT剂量胶片测量电子线百分深度剂量的应用研究

目的 研究EBT剂量胶片在临床电子线百分深度剂量(PDD)中的测量方法.方法 采用14.7 cm×5.1 cm的矩形射野,在同一张EBT胶片上进行5阶梯度的剂量刻度.应用上述刻度方法,针对4、6、8、10、12和15 MeV电子线,在小水箱中采用竖直和倾斜5°两种方式测量PDD,并与半导体探头的三维水箱扫描结果以及平行板电离室在小水箱中测量结果进行比较和分析°结果当剂量胶片上端与水面平齐时,EBT测量的PDD曲线与两种探头测量的结果具有较好一致性,并且倾斜和竖直测量两种方式无明显差异.当剂量胶片上端伸出水面时,在竖自测量方式下剂量建成区内测量结果明显低于其他测量结果,而倾斜测量方式下则无明显影响.结论 新的剂量刻度方式快捷可靠,可显著减少剂量胶片用量.在测量电子线PDD时建议将胶片倾斜一定角度进行,以便减小胶片上端与水面不平齐所引起的测量误差.     

EBT剂量胶片测量电子线百分深度剂量的应用研究

目的 研究EBT剂量胶片在临床电子线百分深度剂量(PDD)中的测量方法.方法 采用14.7 cm×5.1 cm的矩形射野,在同一张EBT胶片上进行5阶梯度的剂量刻度.应用上述刻度方法,针对4、6、8、10、12和15 MeV电子线,在小水箱中采用竖直和倾斜5°两种方式测量PDD,并与半导体探头的三维水箱扫描结果以及平行板电离室在小水箱中测量结果进行比较和分析°结果当剂量胶片上端与水面平齐时,EBT测量的PDD曲线与两种探头测量的结果具有较好一致性,并且倾斜和竖直测量两种方式无明显差异.当剂量胶片上端伸出水面时,在竖自测量方式下剂量建成区内测量结果明显低于其他测量结果,而倾斜测量方式下则无明显影响.结论 新的剂量刻度方式快捷可靠,可显著减少剂量胶片用量.在测量电子线PDD时建议将胶片倾斜一定角度进行,以便减小胶片上端与水面不平齐所引起的测量误差.     

宫颈癌调强放疗膀胱受照剂量的评价

目的:研究宫颈癌调强放疗计划设计中膀胱壁与膀胱受照剂量的差别,从而在计划设计中正确设置和评价膀胱的限制剂量。方法:随机选取19例宫颈癌病例,为其设计调强计划。为了便于比较,分别给19例患者设计第一程全盆照射计划,处方剂量50 Gy/25次,利用DVH图分别评价膀胱和膀胱壁的受量。结果:调强计划中膀胱、膀胱壁的最小剂量、最大剂量差异均无统计学意义。膀胱平均剂量、D70、D50、D40和D30分别为38.45、30.07、38.68、43.90和47.54 Gy,膀胱壁平均剂量、D70、D50、D40和D30分别为40.97、32.80、45.83、49.16和50.24 Gy。用膀胱所受剂量评价膀胱壁剂量,膀胱壁平均剂量、D70、D50、D40和D30分别被低估6.55%、9.08%、18.49%、11.98%和5.68%。结论:在宫颈癌调强计划设计中,简单的用整个膀胱受量评价膀胱壁受量,将会低估膀胱壁的真正受量,从而加大膀胱并发症的概率,对膀胱造成不必要的损伤。     

Accuracy and precision of absorbed dose measurements for neutron therapy

The occurrence of normal tissue complications and probability of tumor control are steep functions of absorbed dose. Consequently the delivery of the dose to the patient should be performed with a precision better than +/- 2% and an overall uncertainty less than +/- 5%. The sequence of dosimetry procedures to deliver the absorbed dose to the patient is analyzed with emphasis on the physical parameters involved in neutron dosimetry; the results of neutron dosimetry intercomparisons are summarized. The protocols for neutron dosimetry formulated by European and American physicists differ in a number of aspects, including the choice of the phantom material. For the treatment of a specific lesion, e.g., a tumor of the floor of the mouth, different treatment plannings have been suggested. Regarding the determination of total absorbed dose at a reference point in a phantom, the required overall uncertainty can be achieved for neutron energies up to 20 MeV. Because of differences in size, shape and composition between the phantom and the patient, somewhat larger uncertainties are to be anticipated for the actual treatment. Further experimental and theoretical studies are needed to obtain more reliable values for kerma in different elements and neutron sensitivity of the photon dosimeters for neutron energies in excess of 20 MeV.