Dual radiobiological interpretations of retrospective clinical data: the time factor

Dual interpretations are different radiobiological mechanisms that explain theoretically the same observed results. Radiobiological interpretations of the time factor are most frequently based on changes in total dose that produce a given effect. If this dose is increased by different mechanisms (e.g. increasing overall time and decreasing dose per fraction) at the same time, proposals for altered fractionation schemes based on the choice of one or the other mechanism, in principle, can lead to erroneous predictions of outcome. This is especially the case when the analyses are based on retrospective clinical data, where the influence of patient selection is unknown. Examples of dual interpretations taken from the literature on head and neck, melanoma and prostate cancer are discussed.     

Dual radiobiological interpretations of retrospective clinical data: the time factor

Dual interpretations are different radiobiological mechanisms that explain theoretically the same observed results. Radiobiological interpretations of the time factor are most frequently based on changes in total dose that produce a given effect. If this dose is increased by different mechanisms (e.g. increasing overall time and decreasing dose per fraction) at the same time, proposals for altered fractionation schemes based on the choice of one or the other mechanism, in principle, can lead to erroneous predictions of outcome. This is especially the case when the analyses are based on retrospective clinical data, where the influence of patient selection is unknown. Examples of dual interpretations taken from the literature on head and neck, melanoma and prostate cancer are discussed.     

食管内照射支架的研制及临床应用的初步结果

目的探索食管内照射支架研制、临床使用的可行性、安全性及初步疗效。方法选择合适的覆膜或裸食管支架，于支架外周按一定的规律固定上特制的可容纳放射粒子的鞘，根据患者病变的范围通过治疗计划系统(treatment plan system，TPS)计算出放射粒子的剂量，将放射粒子装进上述鞘内即制成食管内照射支架。临床选择15例食管癌患者，临床分级为Ⅱ～Ⅳ级，将放疗支架植入到患者病变食管内并进行临床随访。结果15例患者内照射支架均释放到位，释放过程顺利，释放过程中未出现放射粒子脱落现象；全身γ射线显像(ECT)复查未发现非靶器官显像；患者全身一般状况明显好转，血象和免疫指标亦未见明显变化，未出现如食管穿孔、出血等并发症；13例术后1个月CT复查提示病灶的厚度较术前变簿，2例变大，3例随访近8个月，CT复查病变厚度较术前明显变薄，胃镜检查并活检提示支架捆绑粒子部位肿瘤明显缩小，活检未发现肿瘤细胞生长。结论食管内照射支架临床使用是安全、可行、有效的，其临床长期疗效需进一步随访观察及对照研究。     

Infrapopliteal application of paclitaxel-eluting stents for critical limb ischemia: midterm angiographic and clinical results

PURPOSE: To report the midterm (30%, or flow-limiting dissection). Patients were followed up with regular clinical evaluation, and digital subtraction angiography was scheduled at 6 months and 1 year. Life-table analysis and Kaplan-Meier plotting of angiographic and clinical variables were performed. Cox proportional-hazards regression analysis was employed to adjust for various covariates and search for independent adverse predictors of angiographic and clinical outcome. RESULTS: Infrapopliteal procedures were performed in 29 patients with 32 limbs with CLI; 79.3% of the patients had diabetes and 34.5% had renal disease. A total of 62 coronary PES were deployed in 50 below-knee lesions (mean stent-implanted length, 25.51 mm+/-12.16). Technical success rate was 100%. The 1-year mortality rate was 16.9%, and the limb salvage rate was 88.5%. The 1-year angiographic in-stent primary patency rate was 30.0%, whereas the incidence of in-stent binary (>50%) restenosis was 77.4%. The 1-year incidence of clinically driven repeat interventions was 30.5%. The Cox model calculated renal disease as the only independent predictor of decreased primary patency and increased repeat intervention events. Initial occlusions also adversely affected primary patency. CONCLUSIONS: Infrapopliteal PES achieved acceptable clinical results in CLI, even though they failed to inhibit vascular restenosis and decrease the need for repeat interventions. Renal disease and initial occlusions are adverse prognostic factors for infrapopliteal endovascular procedures.     

再次椎体成形术的应用

目的探讨再次经皮椎体成形术(PVP)处理首次PVP术后疼痛不缓解的可行性、方法及疗效。方法骨质疏松症并椎体压缩骨折9例共9节行PVP治疗后疼痛不缓解,其中轻度压缩3例、中度以上压缩6例,包括合并囊性积液4例4节和粉碎性压缩2例2节;椎体转移性肿瘤4例共5节行经皮椎体成形术治疗后2～4个月疼痛复发。均采用再次PVP治疗,术后CT观察PMMA分布状况和有无渗漏,并进行临床疗效评价和观察有无并发症。结果再次PVP技术均成功,再注入PMMA量平均为4．8ml,随访1～18个月,CR10例、PR3例。CT证实椎体周围PMMA渗漏2例,但无一例出现临床症状。2例椎体转移肿瘤分别于再次PVP后4、5个月死亡,但无明显相应病变椎体平面疼痛。结论对骨质疏松性椎体压缩骨折PVP后疼痛不缓解及椎体内转移性肿瘤疼痛复发者,再次PVP的疗效显著。关键技术是经椎弓根穿刺至椎体内致痛区并充分充填PMMA。     

The radiobiological principles of boron neutron capture therapy: A critical review

The radiobiology of the dose components in a BNCT exposure is examined. The effect of exposure time in determining the biological effectiveness of γ-rays, due to the repair of sublethal damage, has been largely overlooked in the application of BNCT. Recoil protons from fast neutrons vary in their relative biological effectiveness (RBE) as a function of energy and tissue endpoint. Thus the energy spectrum of a beam will influence the RBE of this dose component. Protons from the neutron capture reaction in nitrogen have not been studied but in practice protons from nitrogen capture have been combined with the recoil proton contribution into a total proton dose. The relative biological effectiveness of the products of the neutron capture reaction in boron is derived from two factors, the RBE of the short range particles and the bio-distribution of boron, referred to collectively as the compound biological effectiveness factor. Caution is needed in the application of these factors for different normal tissues and tumors.     

Biochemical and clinical experience with real-time intraoperatively planned permanent prostate brachytherapy

PurposeTo evaluate patient characteristics and dosimetric parameters that predict biochemical failure (BCF) after real-time planned low-dose-rate prostate brachytherapy.MethodsFrom 1998 to 2008, a low-risk cohort by National Comprehensive Cancer Network criteria of 341 men with a median followup of 41.6 months was analyzed. This cohort had a median age of 65.1 years, prostate volume of 35.8 cc, and pretreatment prostate-specific antigen of 5.6 ng/mL. Patients had predominately Gleason 6 (95.9%) and T1c (81.3%) disease. About 3.6% of the patients received androgen deprivation therapy. Kaplan–Meier and Cox proportional hazards survival analysis methods were used to analyze predictors of BCF (Phoenix definition).ResultsAt 72 months, freedom from BCF was 91.1% (95% confidence interval = 85.0–94.8). The median D₉₀ was 145.9 Gy, and the median V₁₀₀ was 90.3%. Because of infrequent BCF, the following prostate volume groups were examined: 15–<25, 25–<35, 35–<45, and 45+ cc. Of all possible predictors, only small prostate volume (15–<25 cc group) was significantly associated with BCF (hazard ratio = 8.44, 95% confidence interval = 1.82–39.14, p = 0.007). Using Kaplan–Meier analysis, time to BCF was also significantly increased in the lowest prostate volume 15–<25 cc group with 24.1% failing at 48 months compared with 1.6–5.1% among the other groups.ConclusionsReal-time planned low-dose-rate prostate brachytherapy provides excellent biochemical control as a single-agent treatment for low-risk prostate cancer with 91.1% freedom from BCF at 72 months. Only prostate volume less than 25 cc was an independent predictor of BCF.     

Low dose rate teletherapy using a telecaesium 137 unit radiobiological, physical and clinical considerations

Low dose rate teletherapy aims to combine the supposedly superior results obtained with low dose rate implants with the convenience and staff protection characteristics of external beam therapy. Previous investigators have used telecobalt units to produce dose rates of 1.1 to 1.8 Gy/hr to treat in daily sessions lasting 6-10 hours to total doses of 60-70 Gy. These studies have not discounted the possibility that much of the advantage of interstitial implants results from the low dose rates used per se, and from the fact that the total dose is delivered in a short overall time. The relationship between total dose, dose rate and volume giving normal tissue and anit-tumour effects, however, remains ill-defined. At the Newcastle Mater Misericordiae Hospital a Caesium teletherapy unit has been modified to treat at low dose rates and a study has been designed with a view to establish which permutations of total dose and dose rate are isoeffective for acute mucosal and acute skin reactions in the dose rate range between 0.8 and 9.6 Gy/hr (1.3 and 16 cGy/min).     

Autograft meniscus replacement: Experimental and clinical results

Because of the risks related to allograft meniscus replacement an attempt was made to replace the medial meniscus by autograft tissue. In animal experiments the free middle third of the patellar tendon was transformed to a meniscus-like structure within one year after insertion. Early arthroscopic results after autograft meniscus replacement in a clinical series comprising 20 patients are promising.     

PPH手术在临床中的应用

目的 探讨PPH手术适应证及术后并发症的处理。方法 施行PPH手术患者共10例,其中Ⅲ-Ⅳ度痔8例,混合痔伴部分直肠黏膜脱垂2例。结果 所有患者术后便血及直肠黏膜脱垂症状消失,2例术后出现短时间间断性性腹痛,经对症治疗后症状消失。结论 PPH手术是临床上治疗直肠黏膜脱垂及重度痔方法之一,较之传统方法具有明显优点,应在临床中普及推广。     

The potential of ytterbium 169 in brachytherapy: a brief physical and radiobiological assessment.

Ytterbium 169 (half-life 32 days; mean gamma emission 93 keV, after excluding photons of energy less than 10 keV) is a radionuclide with interesting potential for brachytherapy applications. Although not yet commercially available, its possible application as a clinical radionuclide is currently being considered by Amersham International. This article presents an assessment of some properties of the nuclide that may be clinically relevant. Use is made of some new ideas that allow quantification of the likely dose homogeneity that can be obtained in a brachytherapy distribution, and in this context ytterbium 169 is shown to be superior to some currently available brachytherapy nuclides. The assessment also uses recent extensions to the linear-quadratic model to consider the likely radiobiological implications associated with the use of the nuclide. From this it is suggested that the main potential for ytterbium 169 would be as a source that may be re-used for a number of short-term applications, rather than as a permanently implantable nuclide.     

The radiobiological effectiveness of carbon-ion beams on growing neurons

Purpose: Recently carbon-ion beams have been reported to be remarkably effective for controlling various cancers with less toxicity and are thought to be a promising modality for cancer treatment. However, the biological effect of carbon-ion beams arising on normal neuron remains unknown. Therefore, this study was undertaken to investigate the effect of carbon-ion beams on neurons by using both morphological and functional assays.

Materials and methods: Dorsal root ganglia (DRG) and sympathetic ganglion chains (SYMP) were isolated from day-8 and day-16 chick embryos and cultured for 20 h. Cultured neurons were exposed to carbon-ion beams and X-rays. Morphological changes, apoptosis and cell viability were evaluated with the Growth Cone Collapse (GCC), Terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyUridine TriPhosphate (dUTP) nick End Labeling [TUNEL] assay and 4-[3-(4-iodophenyl)- 2-(4-nitrophenyl)- 2H-5-tetrazolio]- 1,3-benzenedisulfonate [WST-1] assays, respectively.

Results: Irradiation caused GCC and neurite destruction on a time- and irradiation dose-dependent manner. Changes in morphological characteristics were similar following either irradiation. Morphological and functional assays showed that day-8 neurons were more radiosensitive than day-16 neurons, whereas, radiosensitivity of DRG was comparable to that of SYMP. The dose-response fitting curve utilising both GCC and TUNEL labeling index showed higher relative biological effectiveness (RBE) values were associated with lower lethal dose (LD) values, while lower RBE was associated with higher LD values.

Conclusion: Exposure to high-linear energy transfer (LET) irradiation is up to 3.2 more efficient to induce GCC and apoptosis, in early developed neuronal cells, than low-LET irradiation. GCC is a reliable method to assess the radiobiological response of neurons.     

The radiobiological and physical basis for radiotherapy with protons and heavier ions

Heavy charged particles exhibit a superior dose distribution compared to all conventionally used beams. The small lateral and range straggling, combined with an increase of the dose deposition with increasing penetration depth enables the production of dose profiles shaped precisely to the contours of the treatment volume. In addition, heavy ion beams exhibit an elevated biological efficiency close to the end of the particle range. Therefore, beams of heavy ions deliver a high physical dose combined with a high biological efficiency to a tumor volume while the surrounding healthy tissue is maximally spared.     

Virtual colonoscopy: clinical application

Virtual colonoscopy (VC), also known as computed tomography Colonography (CTC), is a non-invasive test for the examination of the colon based on volumetric, thin-collimation CT acquisition of a cleansed and air-distended colon. The technique is easy, less labour-intensive than barium enema and conventional colonoscopy, and is inherently safer. Several studies demonstrate the ability of VC in the detection of colonic neoplastic lesions, not only large carcinomas, but also polyps. Currently, the most widely accepted clinical indication is incomplete or unsuccessful colonoscopy, which may be the result of redundant colon, patient intolerance to the procedure, spasm not resolving even with the use of spasmolytics, obstructing colo-rectal cancer. VC is also used to detect cancer in frail and immobile patients to avoid sedation during colonoscopy or the turning required during barium enema. The use of VC in patients under surveillance following colo-rectal cancer surgery is under investigation. Further studies are necessary in order to assess the cost-effectiveness of this approach. For colo-rectal cancer screening, a practical approach is to consider VC as a currently credible alternative screening method and as a reasonable alternative to the other colo-rectal cancer screening tests when a patient is unable or unwilling to undergo conventional colonoscopy.     

磁共振泌尿系造影的相关技术和临床应用探讨

目的评价磁共振泌尿系造影（ＭＲＵ）的成像技术对揭示尿路梗阻部位及原因的价值和限度，并推广应用半傅立叶转换快速自旋回波序列（ＦＡＳＥ）行ＭＲＵ检查的技术方法。方法１８例尿路梗阻、８例非尿路梗阻性疾患及５例健康志愿者，应用ＦＡＳＥ技术行ＭＲＵ检查。无尿路梗阻者１３例检查前口服速尿２０ｍｇ。所有图像后处理均采用最大信号强度投影（ＭＩＰ）技术。结果尿路梗阻病人均能显示梗阻部位和程度，诊断敏感率达１００％，诊断正确率为８３％（１５／１８）。口服速尿增强ＭＲＵ提供了良好的肾脏形态和尿路解剖结构。结论ＭＲＵ是一种方便快捷的技术，可提供高分辨尿路图像     

Pulsed-spray pharmacomechanical thrombolysis: preliminary clinical results

Pulsed-spray pharmacomechanical thrombolysis was used to treat 41 patients with 47 complete thrombotic occlusions of hemodialysis grafts (n = 29), arterial bypass grafts (n = 10), or peripheral native arteries (n = 8). The procedure involves the use of small pulses of highly concentrated urokinase, which are forcefully sprayed throughout the thrombus during systemic heparinization. Virtually complete lysis was achieved in 46 of 47 occlusions. In the 46 thrombi that lysed, mean time for completion of lysis was 63 +/- 35 min and initial partial return of flow required 26 +/- 18 min. Complications included small peripheral emboli in one treated bypass graft (which cleared promptly after further pulse-spray therapy) and bleeding in three cases (one case of hematoma in the infused field at the site of recent surgery, one case of bilateral hematomas at the femoral puncture site, and one minor delayed self-limited gastrointestinal hemorrhage). Results to date suggest that the pulsed-spray pharmacomechanical method augments the speed, consistency, safety, and cost efficacy of clinical thrombolysis. Further study is warranted.