The impact on quality of life by radiation late effects

The Radiation Therapy Oncology Group (RTOG) is developing an improved scoring system for the late effects of radiation therapy. There is a need to assess the impact of treatment on long-term survival. The RTOG Late Effects Toxicity Grading Scale documents the absence or the degree to which a symptom or sign is present. The scale in itself does not, however, score the impact of symptoms on survival. This Late Effects Scale in conjunction with quality-of-life assessments will provide the information necessary to assess the impact of treatment toxicities on normal daily living. Neither documentation of late effects nor their impact on quality of survival is an end in itself. These scales are only instruments that should serve to direct us toward our higher goal of designing interventional studies concerned with the quality of survival or rehabilitation. The development of the Late Effects Toxicities Grading Scale is a beginning.     

Improving intensity-modulated radiation therapy quality assurance by adopting statistical process control

PurposeTo use statistical process control for intensity-modulated radiation therapy (IMRT) quality assurance (QA) and improve tolerance limits and action limits.MethodsAn electronic portal imaging device (EPID) was selected to verify IMRT QA. The I-chart and the exponentially weighted moving averages (EWMA) chart were used to analyze the corresponding results.ResultsTwenty samples were used to enable the sampling requirements for building the control limits to be met. The I-chart showed that isolated data points beyond the control limits were mainly derived from complex plans. The EWMA made predictions of systematic errors earlier than the I-chart. Systematic errors primarily originated from the dose calibration on the EPID, and recalibrating the EPID could eliminate such errors.ConclusionStatistical process control is an effective tool to detect controllable and can be used in IMRT QA. After calibrating the EPID, the tolerance and action limits all improved and satisfied the requirements/recommended values of the AAPM TG-218 report.     

Improving quality of patient care by improving daily practice in radiation oncology

Radiation oncology is an ever-advancing, complex, technologically based specialty that has been thrust into the public spotlight because of recent reports of serious treatment delivery errors that have impacted the quality of patient care. Although quality assurance (QA) initiatives are already common place in radiation oncology, the continued complex technology and automation-based advances in radiotherapy have created new safety challenges. The ongoing evolution of safety challenges in radiation oncology requires corresponding evolution in workflow and QA programs to ensure the quality of patient care. We believe that the incorporation of QA themes into our daily practice will help to create safer patient environments. Practical QA approaches that can be readily incorporated and applied in the daily practice of radiation oncology include process engineering and human factors engineering, medical peer review, "safety rounds," and software QA tools. Most importantly, we need to develop a culture of safety in which all team members work together to maximize the quality of our patient care.     

Direct aperture optimization as a means of reducing the complexity of intensity modulated radiation therapy plans

Background

To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT).

Methods

Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30–70 Gy) and minimum, mean rectal doses were assessed.

Results

Median age was 69 years. Percentage of rectal volume receiving high doses (≥ 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving ≥ 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02).

Conclusion

Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (≥ 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.     

A method for studying nasal air flow by means of fluid dynamics experiments

We present a simple but effective and exemplary method for investigating the basics and principles of complex nasal air flow patterns. Fluid dynamics experiments are one informative way for studying physiology and pathophysiology of nasal breathing. For in-vivo investigations sufficient visualisation of nasal air flow appears to be impossible. Experiments need to be done on transparent models with a suitable streaming medium and good visualisation of stream lines. We present an experimental arrangement for studying nasal air flow pattems with anatomically correct nasal models which were obtained by taking casts from nasal cavities of corpses and patients as well as in functional models. Water proved to be an appropriate streaming medium. Controlled flow through the model was produced through a suction pump connected to the nasopharyngeal side of the nasal model. Visualisation of streamlines and flow patterns was obtained using dyes or small bubbles as markers. Physiological inflow and outflow requirements were simulated by placing the model into a huge reservoir of water. Results from experiments with these models can – with some limitations – lead to conclusions for air flow behaviour in the human nose.     

Manipulations in the oxygen transport capacity of blood as a means of sensitizing tumors to radiation therapy

Tumor response to radiation is dependent not only on the quantity of hemoglobin (Hb) available for oxygen (O2) transport but also on the position of the Hb-O2 dissociation curve (Hb affinity). Previous studies have shown that administering agents which shift the Hb-O2 dissociation curve to the right (decrease Hb affinity) sensitize tumors to radiation by reducing the fraction of radiobiologically hypoxic cells. However, there may be toxicity limitations when agents aimed at altering Hb affinity are administered directly to the host. The present studies evaluated the therapeutic benefit of shifting the Hb-O2 dissociation curve in vitro prior to the transfusion of the biochemically modified RBCs into recipient hosts. Mice were given a hemolysis agent (phenylhydrazine hydrochloride, PH) prior to transfusing RBCs with normal or altered Hb affinity. A 100 mg/kg dose of PH reduced the hematocrit to approximately 60% of control 24 hr after treatment. Tumors irradiated at this time demonstrated an increased fraction of hypoxic cells. If the hematocrit was returned to normal by transfusing mice prior to irradiation, a significant but transient reduction in the hypoxic fraction was seen. Tumor response was reduced if RBCs with elevated Hb affinity, obtained by storing the erythrocytes at 4 degrees C, were used. Alternatively, tumor sensitization was noted when animals were transfused with RBCs having decreased Hb affinities. The latter was achieved by incubating the RBCs in the presence of either clofibrate or the precursors of 2,3 diphosphoglycerate (2,3 DPG). These findings further support the notion that the Hb affinity is an important parameter in determining tumor response to radiation and suggest that this factor ought to be considered when RBCs are used to transfuse anemic patients undergoing radiotherapy.     

Chronic pain control by means of an epidural catheter: report of a case with description of the method.

The feasibility of long-term epidural catheterization for control of chronic pain from sacral metastases has been demonstrated. Infection was not a problem and obstruction of the catheter did not occur. The short duration of action of currently available drugs was the major limitation of the technique. The technique described merits further investigation as an alternative to currently available methods.     

Detection of p53 mutations in gynecologic tumors by means of a simple, nonradioactive minigel method of PCR-SSCP analysis

We studied 22 gynecological tumors for mutations in exons 5 through 8 of the p53 gene by means of SSCP analysis, using a simplified, nonradioactive technique developed at our laboratory. In order to test the procedure, we carried it out in parallel with the usual radioactive one. Two coincident mutations (in exons 5 and 8) were found by means of both methods. However, an additional one in exon 6 was found by means of our nonradioactive technique. This simplified method for SSCP-analysis of the p53 gene in human tumors is faster, easier and cheaper to perform than the conventional radioactive method, and yields equivalent results. It could be thus an excellent candidate for routine use in the clinical setting.     

逆向计划调强适形放射治疗的质量保证

目的：通过一系列调强验证方法的研究，探讨逆向计划调强适形放射治疗（IMRT）的质量保证方法是否可行。方法：用Varian Cadplan三维治疗计划系统中Helios逆向计划系统对前列腺癌、鼻咽癌、脑瘤、胰腺癌、椎骨转移癌等设计并进行IMRT。为验证计划系统生成的各个照射野注量图与实际注量图的一致性，将剂量胶片放在平板有机玻璃体模下，使计划中的各个照射野始终垂直于体模表面；调用患者治疗数据分别单独照射，冲洗胶片后与计划得出的注量图进行比较。将剂量胶片夹在仿真体模适当的部位，调用患者治疗数据对体模进行模拟照射，由此得出轴向截面上的等剂量分布，与计划的等剂量曲线拟合比对。用电离室和水箱验证等中心和偏离点的绝对剂量。在模拟机或加速器上拍正侧位照射野验证片，与CT模拟数字重建的射线影像片比较，验证等中心位置。结果：各射线束轴垂直方向测得的注量图与计划系统计算的一致；等中心点绝对剂量测量的结果与计划计算的误差在3％以内，偏离点绝对剂量误差较大；轴向截面等剂量曲线分布的胶片测量结果与计划计算的很接近；等中心位置误差在3mm以内。结论：近一年的实践证明在IMRT中所采用的上述质量保证措施是切实可行的。     

Measuring the quality of care in radiation oncology

Quality care is one of the dominant issues in health care today. In this article, we will review the key concepts underlying quality measures and discuss how measures are developed and defined. We will next examine how these measures are currently being used and will conclude with some thoughts regarding the steps necessary to use quality measures to improve the quality of care in radiation oncology.     

Isogenic normal basal and luminal mammary epithelial isolated by a novel method show a differential response to ionizing radiation

Epithelial cells within the normal breast duct seem to be the primary target for neoplastic transformation events that eventually produce breast cancer. Normal epithelial cells are easily isolated and propagated using standard techniques. However, these techniques almost invariably result in populations of cells that are largely basal in character. Because only approximately 20% of human breast cancers exhibit a basal phenotype, our understanding of the disease may be skewed by using these cells as the primary comparator to cancer. Further, because germ line mutations in BRCA1 yield breast cancers that are most often of the basal type, a comparison of normal basal and luminal cells could yield insight into the tissue and cell type specificity of this hereditary cancer susceptibility gene. In this report, we describe a simplified and efficient method for isolating basal and luminal cells from normal human breast tissue. These isogenic cells can be independently propagated and maintain phenotypic markers consistent with their respective lineages. Using these cultured cells, we show that basal and luminal cells exhibit distinct responses to ionizing radiation. Basal cells undergo a rapid but labile cell cycle arrest, whereas luminal cells show a much more durable arrest, primarily at the G(2)-M boundary. Molecular markers, including p53 protein accumulation, p53-activated genes, and BRCA1 nuclear focus formation all correlate with the respective cell cycle responses. Further, we show that short-term cultures of human breast tissue fragments treated with ionizing radiation show a similar phenomenon as indicated by the biphasic accumulation of p53 protein in the basal versus luminal layer. Together, these results indicate that normal basal cells have a transitory cell cycle arrest after DNA damage that may underlie their increased susceptibility to transformation after the loss of functional BRCA1.     

Cerebellar medulloblastoma: results of a new method of radiation treatment.

Nine patients with medulloblastoma were referred to the Radiation Oncology Section at the University of Chicago from 1966 to 1976. In all patients, the tumor was situated in the posterior cranial fossa, projecting from the cerebellum into the fourth ventricle. After partial tumor resection and histological diagnosis, radiation treatment was instituted: a localized dose of 1000 rad to the posterior fossa through lateral opposing ports and a total dose of 4000-5000 rad through the "hockey-stick" port to the entire CNS. With this treatment, 9 patients yielded actuarial 3- and 5-year survival rates of 88% and 73%, respectively. Five of the patients possessed no history of neurologic or spinal growth deficits after treatment. Two patients had a slight retardation of spinal growth. The remaining patients had presented symptoms of a tumor mass in the posterior fossa for a period of over 8 months prior to treatment. They were found at craniectomy to have diffuse intracranial tumor involvement, and their survival times deteriorated rapidly. The "hockey-stick" port provided a uniform distribution of radiation exposure to the entire brain and spine. It was simple to use and posed little inconvenience to patients in the pediatric age group.     

Error in the delivery of radiation therapy: results of a quality assurance review

PURPOSE: To examine error rates in the delivery of radiation therapy (RT), technical factors associated with RT errors, and the influence of a quality improvement intervention on the RT error rate. METHODS AND MATERIALS: We undertook a review of all RT errors that occurred at the Princess Margaret Hospital (Toronto) from January 1, 1997, to December 31, 2002. Errors were identified according to incident report forms that were completed at the time the error occurred. Error rates were calculated per patient, per treated volume (>/=1 volume per patient), and per fraction delivered. The association between tumor site and error was analyzed. Logistic regression was used to examine the association between technical factors and the risk of error. RESULTS: Over the study interval, there were 555 errors among 28,136 patient treatments delivered (error rate per patient = 1.97%, 95% confidence interval [CI], 1.81-2.14%) and among 43,302 treated volumes (error rate per volume = 1.28%, 95% CI, 1.18-1.39%). The proportion of fractions with errors from July 1, 2000, to December 31, 2002, was 0.29% (95% CI, 0.27-0.32%). Patients with sarcoma or head-and-neck tumors experienced error rates significantly higher than average (5.54% and 4.58%, respectively); however, when the number of treated volumes was taken into account, the head-and-neck error rate was no longer higher than average (1.43%). The use of accessories was associated with an increased risk of error, and internal wedges were more likely to be associated with an error than external wedges (relative risk = 2.04; 95% CI, 1.11-3.77%). Eighty-seven errors (15.6%) were directly attributed to incorrect programming of the "record and verify" system. Changes to planning and treatment processes aimed at reducing errors within the head-and-neck site group produced a substantial reduction in the error rate. CONCLUSIONS: Errors in the delivery of RT are uncommon and usually of little clinical significance. Patient subgroups and technical factors associated with errors can be identified. The introduction of new technology can produce new ways for errors to occur, necessitating ongoing evaluation of RT errors for quality assurance. Modifications to processes of care can produce important reductions in error rates.     

Development of a novel method to enhance the therapeutic effect on tumours by simultaneous action of radiation and heating

Abstract

Purpose: This paper describes the development of a new type of electromagnetic hyperthermia applicator delivering dose control within large application fields and increased effectiveness by providing simultaneous action of radiation and heating (SRH) in malignant tumours, and development of a dosimetric feedback method to support SRH. Materials and methods: Single and phased arrays of flexible applicators have been developed to allow simultaneous hyperthermia and external beam therapy. A frequency of 434?MHz is used to heat near-surface and moderately deep-seated tumours and 70?MHz for deep-seated tumours. Phase and amplitude control allows focusing of electromagnetic energy (EM) to deep-seated tumours. The specific absorption rate (SAR) dose distribution can be modified to achieve uniform heating of tumours with complex shapes and heterogeneous tissue properties. A lithium fluoride thermoluminescent dosimeter (TLD) in a flexible film cassette has been developed for real-time dose measurement. Results: Four types of 434?MHz applicators were manufactured with 3, 4, 9 or 12 independent applicators. Two types of 70?MHz applicators were made with 4 or 6 independent applicators. Phantom tests demonstrated the ability to control the SAR pattern by phase and amplitude control. Placement of the dosimeter between bolus and phantom increased the phantom surface temperature up to 3?°C and showed that the ratio of absorbed energy in TLD to dose in water approaches (0.83?±?3%) for photon energies >60?keV. Conclusions: Simultaneous and controlled radiation and local hyperthermia is technically feasible in a preclinical setting, a clinical feasibility test is the next step.     

Analyzing incidence of testis cancer by means of a frailty model

There are two striking epidemiological features of testicular cancer. First, the incidence has increased strongly over the past few decades. Secondly, the incidence is greatest among younger men, and then declines from a certain age. We have constructed a statistical model to fit these observations. The idea of the model is that a subgroup of men is particularly susceptible to testicular cancer. In statistical terminology this is called a frailty model, since it focuses on varying frailty of the individuals. The frailty, or susceptibility, is considered as being established by birth, and due to a mixture of genetic and environmental effects. The strong increase in incidence over calendar time points to strong environmental effects, which are thought to operate in fetal life, causing damage to the fetus. Based on data from the Norwegian Cancer Registry we fit a frailty model to incidence data collected during 1953–93. The model gives a good fit and we discuss the interpretations of our findings.