Control Probability Research Articles

Embedded Memories Fault-Tolerant Pre- and Post-Silicon Optimization

This paper proposes a structured method for scaling both the supply voltage as well as the body bias voltage for CMOS embedded static memory with the aim of achieving a controllable and dynamic probability of failure with minimum power consumption for each memory block. The target error probability is managed according to the time varying error tolerance attributes of the application using the memory at a certain instant in time. This approach enables system designers to abstract the concepts of power awareness, yield and reliability as design tradeoffs-that incorporate application knowledge-early in the design cycle. The paper develops a formal theoretical and practical foundation based on the underlying device statistics upon which both system and circuit designers can investigate error aware design.

Abstract 2669: Radiosensitizing effect of intratumoral mIL-12 electrogene therapy in murine sarcoma

Abstract Due to the limited success rate of conventional therapeutic approaches to soft tissue sarcomas, new treatment modalities, such as gene therapy, are being evaluated as adjuvant therapies to conventional methods. Electrogene therapy with interleukin-12 (IL-12) has been proved very effective due to the induction of adaptive immunity and innate resistance as well as anti-angiogenic action. The aim of our study was to evaluate the radiosensitizing effect of single and repetitive intratumoral (i.t.) mIL-12 electrogene therapy (mIL-12 EGT) in murine sarcoma. Solid SA-1 fibrosarcoma tumors were induced in the back of A/J mice by subcutaneous injection of tumor cells. The first therapeutic approach consisted of a single i.t. mIL-12 EGT (20 µg of plasmid DNA), followed by a single dose (10 Gy) or graded doses (2.5 – 70 Gy) of local tumor irradiation 24 h later. In the second therapeutic approach, tumor irradiation was followed by two additional i.t. mIL-12 EGT, on the third and fifth day. The tumor growth delay, complete response rates and local tumor control assay (TCD50 assay) were used as a measure of antitumor effectiveness of the therapies and skin damage in the irradiation field was also scored. Tumor and serum concentrations of cytokines mIL-12 and mouse interferon γ (mIFNγ) were measured using ELISA. Therapies with i.t. mIL-12 EGT demonstrated good antitumor effects in murine SA-1 sarcoma tumors and also a radiosensitizing effect when combined with irradiation. Both antitumor and radiosensitizing effects were more pronounced when using repetitive rather than single i.t. mIL-12 EGT. Single i.t. mIL-12 EGT resulted in 7% complete responses and, when combined with single dose irradiation, it produced a radiosensitizing effect resulting in 21% complete responses. In both cases we also detected significantly elevated levels of cytokines mIL-12 and mIFNγ in tumors but no significant increase of both cytokine levels in the serum. Repetitive i.t. mIL-12 EGT alone resulted in 75% complete responses and, when combined with single-dose irradiation, produced the most pronounced potentiation of the radiation response resulting in 100% complete responses of the treated tumors. The TCD50 value was 30 Gy for irradiation alone, and 13.8 Gy for i.t. mIL-12 EGT combined with irradiation. Therefore, the dose-modifying factor of a single i.t. mIL-12 EGT in murine SA-1 sarcoma was 2.17. At the same level of skin damage, dry desquamation, in combined therapy a 44% higher probability of local tumor control than with irradiation alone was observed. The results of our study demonstrate that i.t. mIL-12 EGT is an efficient treatment modality for treatment of soft tissue sarcoma alone and as adjuvant therapy to single dose irradiation. This is due to its pronounced radiosensitizing effect caused by boosting the immune response of the organism. The dose-modifying factor of a single i.t. mIL-12 EGT in murine SA-1 sarcoma was 2.17. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2669. doi:10.1158/1538-7445.AM2011-2669

Control Limits Based on the Narrowest Confidence Interval

In statistical process control (SPC), if the traditional 3-sigma control limits or probability limits are adopted, some points with relatively high occurrence possibility may be excluded; however, some points with relatively small occurrence possibility may be accepted for asymmetrical or multimodal distributions. Motivated by the highest posterior density credibility interval, we propose control limits based on the narrowest confidence interval to solve the problem, where the narrowest confidence interval denotes the confidence interval with the shortest width. The proposed control limits will not only meet the false alarm requirement, but also ensure that each in-control data point has relatively high occurrence possibility. Some properties of the proposed control limits and its relation to the existing two control limits are presented in the end.

Reliability of construction control of cable-stayed bridges

Deck elevations and cable tensions change throughout the construction process of a long-span cable-stayed bridge. Accordingly, geometric errors of deck elevations and tension errors in cables are frequently encountered. The tolerance values of such errors are of great concern to the construction control of cable-stayed bridges. In order to obtain reasonable tolerance errors of deck elevations and cable tensions, the randomness of geometric parameters, the material parameters and the loading parameters of the bridge during erection should be considered. This paper presents a novel reliability-based approach to determine the tolerance errors for different construction stages of a cable-stayed bridge. In the proposed approach, an improved response surface method based on finite-element analysis of segmental construction of the bridge girder is used to yield the failure probabilities of construction control under different erection errors. Reasonable tolerance errors are then obtained based on the acceptable failure probabilities. For engineering applications, the proposed method is further applied to the reliability analysis of the construction contort of the newly built Huangpu Bridge across the Pearl River in Guangzhou. The new approach is also applicable to the construction control of other types of bridges.

A probabilistic model of the control of technical systems

A model is proposed that describes the consideration of the control of the reliability in renewable systems such that the consideration is applied to determine the moment a system’s failure happens and its repair should take place. The presented model differs from the known models in the fact that the magnitude of the probability of the failure detection is multiplied by the magnitude of the leading function among the functions of the repair probability. The leading function is called the repair resource. Thus, the magnitude of the probability of the correct control determines the magnitude of the repair resource. This means that it also controls the magnitude of the regeneration period for a random process of the repaired system.

Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours

PurposeTo quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark.MethodsSeven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour.ResultsThe average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively.ConclusionsA significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.

An Energy-Efficient Access Control Algorithm with Cross-Layer Optimization in Wireless Sensor Networks

This paper presents a wireless sensor network (WSN) access control algorithm designed to minimize WSN node energy consumption. Based on slotted ALOHA protocol, this algorithm incorporates the power control of physical layer, the transmitting probability of medium access control (MAC) layer, and the automatic repeat request (ARQ) of link layer. In this algorithm, a cross-layer optimization is preformed to minimizing the energy consuming per bit. Through theory deducing, the transmitting probability and transmitting power level is determined, and the relationship between energy consuming per bit and throughput per node is provided. Analytical results show that the cross-layer algorithm results in a significant energy savings relative to layered design subject to the same throughput per node, and the energy saving is extraordinary in the low throughput region.

Radiotherapy in the Treatment of Resectable Rectal Adenocarcinoma

The goal of treatment is to cure whereas maintaining sphincter function and minimizing toxicity. Although the mainstay of the treatment is surgery, radiotherapy (RT) is used in a substantial proportion of patients depending on the location and extent of the tumor. The aim of this article is to discuss the role of RT in patients with resectable rectal adenocarcinoma. This article is a review of the pertinent literature. Results show that patients with T1N0 exophytic, well to moderately differentiated, mobile tumors < or = 3 cm in diameter may be treated with either transanal excision or endocavitary RT. The probability of cure with either approach is approximately 80% to 90% and depends on selection criteria. The advantages of endocavitary RT are that it is an outpatient procedure requiring, at most, local anesthesia and is suitable for elderly, infirm patients. The disadvantage is that few of these treatment units are available. Patients who experience a local-regional recurrence may be surgically salvaged. Patients who undergo transanal excision and have unfavorable pathologic findings including equivocal or close margins, poor differentiation, invasion of the muscularis propria, and/or endothelial-lined space invasion have a high risk of local-regional recurrence after surgery alone. The addition of postoperative RT improves the likelihood of cure from 85% to 90%. Patients presenting with unfavorable tumors that are borderline resectable with a transanal excision may be downstaged with preoperative RT and rendered suitable for a wide local excision. The addition of concomitant chemotherapy probably enhances downstaging and may improve the likelihood of sphincter preservation. Patients with T3 and/or N1 rectal cancers have a relatively high probability of local-regional recurrence after surgery alone. Preoperative RT and postoperative RT combined with adjuvant chemotherapy have been shown to significantly reduce the risk of local-regional recurrence and improve survival. Whether preoperative RT alone or combined with chemotherapy is more efficacious than postoperative chemoradiation remains unclear. Endocavitary RT or transanal excision is suitable for patients with T1N0 cancers. Depending on tumor location and extent, adjuvant RT may improve the probability of local-regional control and survival for patients with locally advanced rectal adenocarcinomas.

The determinants of tobacco control in Europe: A research note

A series of Probit regressions are estimated to assess the determinants of tobacco control laws in a cross-section of European countries. Although significance is sparse amongst several of the variables included in the analysis, we do find a tendency for the probability of tobacco control to be higher in lower income non-EU countries, with larger shares of government health care expenditures.

Comparison of predicted and clinical response to radiotherapy: A radiobiology modelling study

Introduction. A model to predict clinical outcome after radiation therapy would be a valuable aid in the effort of developing more tailored treatment regimes for different patients. In this work we evaluate the clinical utility of a model that incorporates the following individually measured radiobiology parameters: intrinsic radiosensitivity, proliferation and number of clonogenic cells. The hypothesis underlying the study was that the incorporation of individually measured tumour parameters in a model would increase its reliability in predicting treatment outcome compared with the use of average population derived data. Material and methods. Forty-six patients with head and neck tumours were analyzed, the majority of whom received both external beam radiotherapy and brachytherapy. Eighteen patients received external beam treatment alone and statistical analyses were carried out on this subgroup. Results. Four of the 18 patients had a >95% calculated probability of cure and none developed a local recurrence resulting in a negative predictive value of 100% (compared with 67% for population-derived data). The sensitivity of the model in predicting local recurrence was 75% (compared with 38% for population-derived data). Using a model that incorporated individually measured radiobiology data, there was a statistically significant difference in local control levels for patients with >95% and <5% predicted probability of local control (χ2, p = 0.04). Discussion. This study suggests, therefore, that incorporation of measured biological data within a radiobiological model improves its ability to predict radiation therapy outcome compared with the use of population-derived data.

Definitive Radiotherapy for Prostate Cancer

The probability of extraprostatic disease may be estimated based on clinical T-stage, pretreatment prostatic-specific antigen, Gleason score, and percent positive core biopsies. Patients with disease confined to the prostate may be treated with either prostatectomy or radiotherapy (RT). Patients with extraprostatic disease without evidence of distant metastases are best managed with RT. RT consisting of either external beam and/or brachytherapy results in a relatively high likelihood of cure, particularly for those with low- and intermediate-risk disease. The impact of elective nodal RT on survival is unclear. Dose escalation results in improved biochemical relapse-free survival compared with standard dose RT. Androgen deprivation therapy likely improves the probability of disease control in patients with high-risk cancers.

FDG-PET in der Bestrahlungsplanung von nichtkleinzelligen Bronchialkarzinomen

Besides the use of FDG-PET in staging and restaging of patients with non-small cell lung cancer (NSCLC), the integration of PET-data into the radiotherapy planning process is a promising field for PET in radiooncology. The possible benefit of the patients lies in the more exact definition of malignant structures for target volume definition. Especially in cases with post-obstructive atelectasis the use of FDG-PET significantly improves the inter-observer-variability of target volumes. Moreover, the higher diagnostic accuracy in lymph node staging compared to CT could lead to a restriction of irradiation fields to FDG positive areas, if clinical target volume concepts were adapted to the new technologies available. Still unsolved is the problem of which is the best method for technical delineation of PET-based target volumes, as due to resolution and movement effects, the FDG-accumulations appear blurred. Here, possibly contrast-oriented methods are of use. Clinical studies will show the benefit of FDG-PET based target volume definition for patients with NSCLC concerning local control and normal tissue complication probability. The aim is to apply higher radiation doses in more exactly defined volumes, while simultaneously sparing normal tissues.

Optimal treatment margins for radiotherapy of prostate cancer based on interfraction imaging

Purpose. To present a methodology to estimate optimal treatment margins for radiotherapy of prostate cancer based on interfraction imaging. Materials and methods. Cone beam CT images of a prostate cancer patient undergoing fractionated radiotherapy were acquired at all treatment sessions. The clinical target volume (CTV) and organs at risk (OARs; bladder and rectum) were delineated in the images. Random sampling from the CTV-OAR library was performed in order to simulate fractionated radiotherapy including intra- and interpatient variability in setup and organ motion/deformation. For each simulated patient, four treatment fields defined by multileaf collimators were automatically generated around the planning CTV. The treatment margin (the distance from the CTV to the field border) was varied between 2.5 and 20mm. Resulting dose distributions were calculated by a convolution method. Doses to OARs were reconstructed by polynomial warping, while the CTV was assumed to be a rigid body. The equivalent uniform dose (EUD), the tumor control probability (TCP) and the normal tissue complication probability (NTCP) were used to estimate the clinical effect. Patient repositioning strategies at treatment were compared. Results. The simulations produced population based EUD histograms for the CTV and the OARs. The number of patients receiving an optimal target EUD increased with increasing margins, but at the cost of an increasing number receiving a high EUD to the OARs. Calculations of the probability of complication-free tumor control and subsequent analysis gave an optimal treatment margin of about 10mm for the simulated population, if no correction strategy was undertaken. Conclusions. The current work illustrates the principle of optimal treatment margins based on interfraction imaging. Clinically applicable margins may be obtained if a large patient image database is available.

Long‐term results of Molteno implant insertion in cases of chronic angle closure glaucoma

This study was undertaken to provide data on the long-term results of cases of chronic angle closure glaucoma with additional risk factors treated by Molteno implants between 1985 and 2004 at Dunedin Hospital, New Zealand. A prospective non-comparative case series followed 21 eyes (17 patients) for a mean of 5.7 years (range 1.3-16.3 years) in terms of intraocular pressure, visual acuity and subsequent procedures. Insertion of a Molteno implant has controlled the intraocular pressure at 21 mmHg or less in 100% of cases at 5 years after surgery, the probability of control being 0.95 (95% CI 0.91-0.99). The mean number of hypotensive medications reduced from 2.04 (SD 0.92) preoperatively to 1.40, 0.64 and 0.66 at 1, 2 and 5 years, respectively. The mean visual acuity improved from 6/18 preoperatively to 6/12 at 1 year and declined to 6/13.5 at 2 and 5 years. Insertion of Molteno implants was a safe and effective procedure in the management of complex cases of chronic angle closure glaucoma.

SU-FF-T-263: Influence of Implanted Gold Markers On the Dose Distributions for Therapeutic Proton Beam

Purpose: The aim of this work is to examine the influence of implanted gold markers on the dose distributions in proton therapy and to investigate the dependency on the marker position in Spread Out Bragg Peak (SOBP) proton beam. Methods and Materials: The implanted gold marker has a cylindrical shape of 3mm length and 1.2mm diameter. The dose influence of the gold marker was verified in the condition of various locations of the proton beam field, which has 20 cm range in patient and 5cm of SOBP. Spatial dose distributions were measured using 3‐Dimensional moving water phantom and a stereotactic diode detector with 0.5 mm of effective diameter. Also, a film dosimetry using EBT film was performed. For Monte Calro simulation, GEANT4 simulation tool kit was used to confirm the measurement and to simulate the dose influence of multi‐implanted condition. Results:Gold is high‐Z material, which is good for CT marker but give more proton beam divergency and more under‐dosed volume. The under‐dosed volume of cold spots due to the single gold marker is measured to be 0.035 cc which has less than 80% of a prescription dose. The effect on the volume‐dose relation has been studied. Monte Calro simulation made us enable to study the various conditions of marker position. Conclusion: Cold spots inside the target volume affect the probability of the local tumor control. Cold volume due to the gold marker is very small but is not trivial in the view of the local control probability in proton therapy. The position of gold markers and the conditions of the proton beam field give the effect on the dose distribution at the target region implanted gold markers.

Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome of head and neck cancer treated with IMRT

The UICC classification (TNM) represents the validated standard tool to describe tumor extent and includes prognostic information on the probability of disease control. The American Joint Committee on Cancer (AJCC) stage grouping is based on the evaluation of treatment and outcome. Gross tumor volume (GTV) might be more relevant than pure description (TNM) or stage grouping as prognostic factor for local control in head and neck cancer (HNC). Based on the observation of GTV-correlated outcome in our initial HNC patient cohort treated with IMRT, we tested the hypothesis that the GTV is the most reliable predictive tool in HNC outcome. A GTV based volumetric staging system (VS) was introduced, using two volumetric cut-off values (15 and 70 cm3). VS, TNM, and AJCC stages were assessed and correlated with outcome following primary radiation in 172 HNC patients. Analyses were based on Kaplan-Meier survival curves. VS proved to be superior to the TNM/AJCC in predicting outcome. In addition, VS enabled to stratify high- and low-risk patients in advanced TN stages. GTV represented the most important prognostic indicator in HNC treated with IMRT and is recommended to be considered for therapeutic decisions and estimation of outcome.

Three-dimensional conformal versus intensity-modulated radiotherapy dose planning in stereotactic radiotherapy: Application of standard quality parameters for plan evaluation

Purpose: The implementation of intensity-modulated radiotherapy (IMRT) technique into clinical practice is becoming routine, but still lacks a generally accepted method for plan evaluation. We present a comparison of the dose distribution of conformal three-dimensional radiotherapy plans with IMRT plans for cranial lesions in stereotactic radiotherapy. The primary aim of this study was to judge the quality of the treatment plans. The next purpose was to assess the usefulness of several quality factors for plan evaluation. Methods and Materials: Five patients, who were treated in our department, were analyzed. Four had meningioma and one had pituitary adenoma. For each case, 10 different plans were created and analyzed: 2 conventional conformal three-dimensional plans and 8 IMRT plans, using the "step and shoot" delivery method. The first conventional plan was an individually designed beam arrangement and was used for patient treatment. The second plan was a standard plan with the same beam arrangement for all patients. Beam arrangements from the conformal plans were the base for the inversely planned IMRT. To evaluate the plans, the following factors were investigated: minimal and maximal dose to the planning target volume, homogeneity index, coverage index, conformity index, and tumor control probabilities and normal tissue complication probabilities. These quantities were incorporated into scoring factors and assigned to each plan. Results: The greatest homogeneity was reached in the conformal plans and IMRT plans with high planning target volume priority in the optimization process. This consequently led to a better probability of tumor control. Better protection of organs at risk and thereby lower normal tissue complication probabilities were achieved in the IMRT plans with increased weighting of the organs at risk. Conclusion: These results show the efficiency, as well as some limitations, of the IMRT techniques. The use of different quality factors allowed us to assess the dose distribution in more depth.

Exact Cochran–Armitage trend tests: comparisons under different models

Exact methods for small-sample dose–response analyses with binary outcome have been rapidly developed in recent years. For exact conditional approach, nuisance parameters (e.g. the intercept) are eliminated by conditioning on their reduced sufficient statistics (e.g. marginal row totals for the intercept under the logit link). For exact unconditional approach, nuisance parameters, on the other hand, are eliminated by using the ‘worst-case’ scenario. For instance, the p-value is the tail probability maximized overall possible values for the nuisance parameters. The performance of exact conditional and unconditional approaches on more general models including logit, probit, one-hit, and extreme-value are investigated here. Comparisons are conducted using the well-known Cochran–Armitage (C–A) trend test under different model specifications. Our simple empirical studies clearly show that the exact conditional approach is generally inferior to the exact unconditional approach with respect to actual significance level and exact power. When sample sizes are small or control group response probabilities are extreme (i.e. close to 0 or 1), the exact conditional C–A trend test could be significantly conservative and less powerful than the exact unconditional C–A trend test even under the popular logit model. For moderate sample size, we also observe substantial exact power loss for the exact conditional approach under models other than logit model. We demonstrate our findings with a real data set from a toxicological study.

Role of Postradical Prostatectomy Irradiation in Carcinoma of the Prostate.

The indications and results of postradical prostatectomy adjuvant pelvic radiation therapy (6,000 to 6,500 cGy) are reviewed. In patients with positive with positive surgical margins, 80% to 100% local tumor control has been reported; in 42 patients treated at our institution, the 5-year actuarial tumor control rate was 85%. Most authors report higher disease-free survival (DFS) rates in patients receiving adjuvant postoperative irradiation for positive margins (70% to 80% at 5 years and 50% to 70% at 10 years) compared with nonirradiated patients (50% at 5 years and 40% at 10 years). However, more difficult to document and never indisputably reported has been the improvement in overall survival (OS) rates with adjuvant irradiation; the actuarial survival rates, 75% to 80% at 5 years and 45% to 60% at 10 years, are comparable to those of nonirradiated patients. Results have been published on patients with positive pelvic lymph nodes (stage D1) following pelvic irradiation (6,000 to 6,500 cGy). At our institution, the 5-year DFS rates were 60% in 22 patients without extracapsular tumor extension and 20% in 34 patients with perprostatic involvement. In 24 patients with postprostatectomy persistently or subsequently elevated prostatic specific antigen (PSA) levels, preliminary analysis showed initial 79% decrease in PSA level after pelvic irradiation (6,000 to 6,500 cGy), although only 70% of the patients have sustained such decreased levels. Patients with persistent or subsequent elevation of PSA after irradiation have a high incidence of distant metastases (50%). There is a suggestion that patients with elevated PSA levels treated to the pelvic lymph nodes (4,500 to 5,000 cGy), in addition to a boost to the prostatic bed (to a total dose of 6,500 cGy), have better results than patients treated to the prostatic bed only. However, longer follow-up is necessary to definitely ascertain the value of irradiation in these patients. Patients with postprostatectomy isolated, clincally palpable recurrences, when treated with irradiation (to 6,500 cGy), have a high probability of local tumor control (90% in 23 patients) at our institution. There is a suggestion that irradiation of the pelvic lymph nodes, in addition to the prostatic recurrence, yields better results. Unfortunately, approximately 60% of these patients develop distant metastases and have poor rates of survival. In conclusion, adjuvant irradiation plays a major role in patients treated with radical prostatectomy in various clinical situations. Radiation therapy as described is well-tolerated. Additional prospective randomized studies are necessary to better assess the role of irradiation in the treatment of these patients.

Radiation induced brachial plexopathies

A daily challenge for the radiation oncologist is toprescribe the optimal radiation dose that will pro-duce the maximal probability of local tumour con-trol, and, at the same time, minimal risk forcomplications. The radiation dose needed to controltumours is commonly close to that tolerated bynormal tissues. Thus, the level of normal tissuemorbidity will often determine the cure rate that maybe achieved.Both tumour cure and serious normal tissuedamage depend on the extent of cell depopulation.Every clonogenic stem cell has to be killed in thetumour to achieve long lasting tumour control.Clonogenic cells, however, have to survive in normaltissues to avoid serious normal tissue damage.Tolerance doses are not absolute values and theyare different for different tissues.The tolerance dose depends on various biological(patient-related) and treatment-related factors. Topatient-related factors belong e.g. age and obesity.Obesity can affect the development of lymph-oedema [1,2]. Co-morbidities like diabetes, hyper-tension, or collagen vascular diseases [3,4] will alsoinfluence the normal tissue reactions. Treatment-related factors are, e.g. chemotherapy, surgery,radiation quality, irradiated volume, number andsize of fractions and overall treatment time [5].This gives a very complex picture that needs tobe individually assessed before prescribing thetreatment.The time of expression of the cellular injury afterirradiation is variable from one tissue to another.The severe acute reactions in rapidly proliferatingtissues can readily be observed and may thus rapidlyresult in changes in radiotherapy schedules that maybe ‘too hot’. This is not the case for late injuries thatcan occur long after completion of therapy. Latereactions are often defined as side effects that occurafter a latency period of more than six months. Theyare generally caused by depletion of slowly prolifer-ating cells with a slow rate of cell loss and renewal,e.g. in central or peripheral (Schwann cells) nervoustissue [6,7], blood vessels (endothelium) [8,9],dermis (fibroblasts) [10