Tight Margins Research Articles

SU‐FF‐J‐112: Radiobiologically Motivated Margin Prescriptions

Purpose: The celebrated formula of Van Herck et al. prescribes a target margin of at least 2.5 times systematic standard error plus 0.7 times random standard setup error, in order “to ensure a minimum dose to the CTV of 95% for 90% of the patients” (van Herk et al., IJROBP (2000) 47:1121–1135). However, minimum dose is an imprecise and biased surrogate for local control. The question we address is whether this margin formula is consistent with radiobiological principles. Method and Materials: To address this issue we make the connection between outcomes and dose distributions using radiobiological modeling and computer simulations of tumor control probability under varying conditions of systematic and random (fraction to fraction) setup errors. We consider an idealized case of a circular cross‐section tumor which is shifted systematically and randomly with respect to a fixed dose distribution which falls off rapidly within the plane. Tumor control probability (TCP) is simulated using the Webb‐Nahum model. Cohorts of patient treatments were simulated with varying target margins for varying conditions of systematic and random setup shifts. The threshold for a clinically important improvement in TCP was set at 0.01 (absolute). Results: The radiobiological simulations consistently indicate that the dose‐based Van Herk formula produces margins which are unnecessarily large. In our simulations, margins equal to 1.2 times the setup error + 0.7 times the random error consistently produced TCP values which were within 0.01 of the large margin limit. Conclusion: Although the details of the margin prescription depend on the characteristics of the test cases, radiobiological, as opposed to purely dosimetric principles, support using tighter margins around gross tumor volumes than those indicated by the Van Herk equation. This research was partially supported by NIH grant CA85181.

Impact of margin on tumour and normal tissue dosimetry in prostate cancer patients treated with IMRT using an endorectal balloon for prostate immobilization

In IMRT treatment, margin for planning target volume is determined by organ motion and set-up error. The margin width that achieves the desired dose escalation, while minimizing normal tissue exposure is dependent upon patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using an endorectal balloon filled with 100 cc of air. Plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. The prescription dose to prostate and seminal vesicles was 70 Gy in 35 fractions with 15% of bladder allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Margins above 5 mm produced significantly lower mean doses for both prostate and seminal vesicles without affecting TCP. For normal tissues, mean doses, percent volumes above prescription constraints and NTCP increased as a function of margin width, especially when this was 5 mm or above. We conclude that planning with tighter margins of < or =5 mm improves IMRT dosimetry for prostate and normal tissues and is only possible when target localization and/or immobilization devices are routinely used.

Methods for image segmentation should be standardized and calibrated

Methods for image segmentation should be standardized and calibrated

Analysis of Intra-Fractional Variations of Anatomy During Prostate IMRT Treatment

Purpose/Objective: The goal of this study is to quantify the positional and volumetric variations of pelvic anatomy during an IMRT treatment fraction. When tight margins are used in certain pre-irradiation image-guided setup procedures, it is important to know the pattern of target motion and its interaction with surrounding normal organs during irradiation.

Experimental Determination of the Heat Transfer Coefficient of a Plate-Fin Heat Exchanger

Heat transfer in compact plate-fin heat exchangers is augmented by the introduction of complex fin patterns in the channels. Kays and London presented a lot of experimental data for several types of fin configurations, and many authors followed their example with other types of fins. For some fin types, the heat transfer correlation for the Nusselt number cannot be found in literature. Most of the data are given for large scale model fins in good controlled laboratory environments—little data is available for real heat exchangers. A test rig was constructed at Ghent University to verify the performance of several fin types. Measurements were done on a real heat exchanger and not on a large scale model in order to determine the performance under real operational conditions. The measurement setup consists of a hot water circuit and an air circuit with a fan. In the heat exchanger, 40 thermocouples are introduced on the air side and the wall. This way, the convection coefficient of the fins can be determined for a broad range of Reynolds numbers. In the paper the measurement set-up is discussed and the measurements are presented. An in depth error analysis is performed on the measurements. This way a heat transfer correlation is provided with a tight error margin for compact plate-fin air coolers.

Specific volumes of unsaturated phosphatidylcholines in the liquid crystalline lamellar phase

The specific volumes of seven 1,2-diacyl- sn-glycero-3-phosphocholines with symmetric, unbranched acyl chains containing one, four, or six cis double bonds per chain, or with a saturated sn-1 chain and one, four, or six cis double bonds in the sn-2 chain were determined by the neutral buoyancy method. Experiments were conducted in the liquid crystalline lamellar phase over the temperature range from 5 to 35 °C. It is demonstrated that the molecular volume of phosphatidylcholines can be well approximated as the sum of a constant volume of the polar lipid head region and the temperature-dependent volumes of hydrocarbon chain CH 2, CH, and terminal CH 3 groups. A linear dependence of chain segment volumes on temperature was observed. A self-consistent set of partially temperature-dependent volumes is obtained that allows prediction of phosphatidylcholine molecular volumes within very tight error margins.

Design of reactive parasitic elements in electronic beam steering arrays

A new approach for the design of electronic beam steering arrays with reactive parasitic elements is introduced. The method is demonstrated at the example of a circular array formed by capacitively tuned monopoles. The related capacitances are determined straightforwardly and without any need for optimization techniques. The resulting beams are rotatable and maintain their gain and beamwidth within tight margins. Comparisons with NEC2 verify the pattern calculation.

WE-E-J-6C-02: Internal Fiducial Markers Can Assist Dose Escalation in Treatment of Prostate Cancer: Results of Organ Motion Simulations

Purpose: We simulated effects of full (no repositioning) and reduced (using fiducial markers and on‐line repositioning following EPI) uncertainties on dose distributions in PTV, prostate, and organs at risk — bladder and rectum; and evaluated limits for dose escalation if on‐line repositioning is implemented and tight PTV margins are applied. Method and Materials: Three patients' anatomies, with large (68cc), medium (55cc) and small (40cc) prostate volumes were used. PTV margins of 2, 4, 6, 9 and 12mm were tested for a conventional 70Gy/35fr, and dose escalated schedules of 74Gy/37fr and 78Gy/39fr. Setup and organ motion uncertainties were modeled in a stochastic manner to generate a dose population histogram. The outcome of each treatment was then scored based on dose distributions in organs. These have been summarized as equivalent uniform doses (EUD) calculated on survival basis for prostate and effective doses from reduced dose‐volume histograms for bladder and rectum. We deemed dose escalation acceptable as long as the currently observed complication rate was not exceeded. To verify validity of obtained margin prescription, 20 patients were studied with the above simulation methods with acceptable margins only. Results: With reduced positioning uncertainties using fiducials, the dose can be escalated to 78 Gy with a reduced PTV margin of 4mm without compromising tumor control probability. Even if large PTV margins (12mm) were applied and dose was escalated to 78Gy, bladder doses did not exceed tolerance levels. The rectal complication probability is comparable to the currently observed rates or even less if rectal bleeding is proven to show strong volume dependence (parallel model) even treating to 78Gy with 4mm margin. The additional 20 patients studied provided similar results. Conclusion: educed positioning uncertainties using fiducial markers allow us to reduce PTV margin to 4mm and escalate dose to 78Gy with similar or lower rectal toxicity rates.

Practical considerations for electron beam small field size dosimetry

Special care of superficial lesions surrounding critical structures, such as an eye, may require tight margins. When this is the case, small megavoltage electron treatment fields and nonstandard treatment distances become necessary. When the field size is found to be less than the practical range of the electron beam, dosimetric measurements should be performed. This research includes data proving that very small electron fields can be employed for treatment with appropriate beam flatness and penumbra. This is accomplished by first coning down the incident beam to a small field size, then secondly by adding a single lead sheet to the patient’s skin surface. The aperture of the sheet is required to be greater than 2 × 2 cm 2 in size, and must be cut properly to adequately confine the treatment area.

Tighter Margins and Tighter Belts, but Still Treating Patients: The Verdict on the Medicare Modernization Act

Few oncologists were taken by surprise when the Medicare Modernization Act (MMA) became law on January 1, 2005; in fact, an informal poll found that many had already been preparing for it well in advance. Now that the MMA has become law, JOP thought it would be beneficial to look at the real-world consequences on patients and practices. JOP also wanted to explore some of the strategies oncologists are using to adapt their practices. Since there is no such thing as a “typical” oncology practice, JOP selected three as representative: a Kansas City, Kansas practice with 35 oncologists, an Albuquerque, New Mexico practice with 11, and one in Paducah, Kentucky with three oncologists. All three practices serve commercial and Medicare patients in urban and rural areas. Two of the three, Kansas City and Albuquerque, are the largest in their respective states. The similarities between all three are as remarkable as the differences.

Tighter Margins and Tighter Belts, but Still Treating Patients: The Verdict on the Medicare Modernization Act

Few oncologists were taken by surprise when the Medicare Modernization Act (MMA) became law on January 1, 2005; in fact, an informal poll found that many had already been preparing for it well in advance. Now that the MMA has become law, JOP thought it would be beneficial to look at the real-world consequences on patients and practices. JOP also wanted to explore some of the strategies oncologists are using to adapt their practices. Since there is no such thing as a “typical” oncology practice, JOP selected three as representative: a Kansas City, Kansas practice with 35 oncologists, an Albuquerque, New Mexico practice with 11, and one in Paducah, Kentucky with three oncologists. All three practices serve commercial and Medicare patients in urban and rural areas. Two of the three, Kansas City and Albuquerque, are the largest in their respective states. The similarities between all three are as remarkable as the differences.

Main contractor experiences of partnering relationships on UK construction projects

Partnering provides a major opportunity for improving project performance, whilst offering direct benefits to the whole of the supply chain. Many research studies reinforce this assertion although there is less critical analysis examining the nature of partnering in practice and whether the claims made for it are consistently justified. The experiences of commercial surveyors and managers within the UK construction industry have been gathered in a pilot study, drawing on the opinions of 48 commercial managers employed by a leading national contractor. The perceptions and experiences of partnering relationships are generally positive, although the early optimism at the beginning of such arrangements is seldom sustained throughout the project lifecycle. Attitudes to partnering are similar whether the relationship is upstream (client/main contractor) or downstream (main contractor/subcontractor). The growth in popularity of alternative procurement methods and statutory adjudication are both regarded as having placed contracting parties on a more equal footing. However in today's competitive environment, contractors continue to operate on tight margins and, common to all project stakeholders, the financial imperative remains the commercial manager's principal consideration. Trust is hard‐earned and relationships are still characterised by a cost driven agenda.

Image-guided radiotherapy for prostate cancer by CT–linear accelerator combination: Prostate movements and dosimetric considerations

Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous "margin" is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of > or =3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer using intensity-modulated radiotherapy with 5-mm margin coverage from the clinical target volume (prostate gland) was performed. With a posterior shift of 10 mm for the prostate, the dose coverage dropped from 95-107% to 71-100% coverage. We have described a technique that corrects for the daily prostate motion, allowing for extremely precise prostate cancer treatment. This technique has significant implications for dose escalation and for decreasing rectal complications in the treatment of prostate cancer.

Optic nerve sheath meningiomas

Optic nerve sheath meningiomas (ONSMs) grow slowly and, if untreated, patients may have stable visual function for up to several years. Treatment of an ONSM may lead to vision loss (radiation retinopathy or optic neuropathy). Therefore, observation is recommended for a patient with ONSM and relatively preserved visual acuity, color vision, pupils, and visual fields. Follow-up every 4 to 6 months initially is recommended extending to annual examinations if visual function and tumor size remain stable for a few years. Neuroimaging can be repeated every 12 months. An undisputed decline in visual function or any intracranial extension warrants treatment of the ONSM. The treatment of choice for a tumor confined to the orbit is stereotactic fractionated radiation. Stereotactic fractionated radiation uses multiple small doses of radiation using tight margins. A reasonable alternative, three-dimensional conformal fractionated radiation uses computed tomography-guided planning but usually requires wider margins. Conventional radiation uses much wider margins and would not be recommended for treatment of ONSM. The radiation can be administered during 5 to 6 weeks in 28 daily fractions of 1.8 to 2 Gy/fraction to a total of 50.4 to 56 Gy. Many patients have improvement or stabilization of their visual function. Gamma knife radiosurgery does not have a role in ONSM because the required dose is toxic to the optic nerve. A tumor that extends intracranially may be treated with fractionated radiation if any vision remains. Surgical excision can be considered for significant intracranial extension but this often leads to complete vision loss in the ipsilateral eye. A blind, disfigured eye also may be treated with en bloc surgical resection of the meningioma.

Constructing markets for temporary labour: employment liberalization and the internationalization of the staffing industry

Abstract Temporary staffing has joined the ranks of the globalizing service industries. The largest agencies have now established a presence in more than sixty nations, where they are placing employees in temporary positions across a range of occupations, from clerical, cleaning and light industrial work through to accountancy, law and IT. The opening up of new occupational and geographical markets around the world has been driven by the imperative to sustain growth in sales volumes, in this business of tight margins and fierce competition. The most lucrative of the staffing industry's ‘emerging markets’ are found in the actively deregulating economies of the global North ‐ including Spain, Germany, Italy and Japan. While exploring how the staffing industry has been active in the construction of these markets, we argue that this fast‐growing business has become an important agent of labour market liberalization.

Image guided radiation therapy

HIGH precision radiation therapy is based on the fact that the tumor and normal surrounding structures have to be delineated in all three dimensions before the radiation oncologist plans the treatment for the patient. The three dimensional computerized treatment planning system then generates a plan in which the tumor gets a high dose and the normal tissues around it get a very low dose of radiation. The radiation is then delivered using a linear accelerator with a multi leaf or micro multi leaf collimator. This methods results in higher cure rates and minimal normal tissue complications. Based on this premise the modern radiation therapy techniques viz. stereotactic radiotherapy, stereotactic radiosurgery, 3 dimensional conformal radiation therapy (3D CRT), and intensity modulated radiation therapy (IMRT) have been developed and have become standard of care in modern radiation therapy departments around the world, including India. Such treatments are planned using CT/ MRI imaging. Till a decade ago the planning techniques were different because the planning was done based on fluoroscopy and not on CT/MRI images. This resulted in two and not three dimensional delineation of tumor and normal tissues and therefore the radiation portals were large so that there was no geographical miss of the tumor. This, however, resulted in inclusion of a larger volume of normal surrounding tissues and the radiation oncologists had to keep the total dose to a lower level in order to keep the complication rates low, but the lower tumor doses were not sufficient enough to result in higher cure rates. When the intention is to spare the normal tissues and the delineation is in three dimensions, the radiation oncologist uses a very tight margin around the tumor which helps in escalating the total tumor dose. This philosophy is utilized in all the modern treatment techniques mentioned above. It has been observed and documented over the last few years that all the organs in the body move during the radiation treatment and also over a period of 4-6 weeks over which all the radiation therapy treatments are delivered. This observation has led us to think that if the

Supply network dynamics as a source of new business

Supply networks where operational control extends well over organizational boundaries have emerged in industries producing relatively complex and customized products with tight profit margins. Products like ships, automobiles and telecommunication systems incorporate complex design and engineering skills that are produced through a tier-structured, multi-level supply networks. Efficiency in these networks has stemmed from specialization and cost efficiency in individual value adding operations. This paper demonstrates how supplier networks have evolved and how the inherent dynamics of these networks generate constantly new business opportunities for fast moving companies with a clear focus on operational efficiency. We use action research methodology on cases from the shipbuilding and constructions industry to document some of the dynamic features of supply networks. This insight is then applied to the electronics manufacturing services business to explain the fundamentals of successful operations in this highly competitive business with ever narrowing margins. In this dynamic market of contract manufacturing companies with constant focus on the reduction of production lead times by incorporating value added operations either physically or logically to maintain and recreate profitable business. To succeed in doing this, issues related to industrial parks, local tacit knowledge and reverse/repair logistics must be managed in cross-organizational manner. We conclude that there is an ever-changing limit to the expansion of supplier networks through specialization and cost efficiency, and that at one point contracting and integrating parts of the supply network will create operationally outperforming business models that further boost the inherent dynamics of supply networks.

Comparison of bat system and a new 3D trans-abdominal ultrasound-based image-guided system for prostate daily localization during external beam radiotherapy

Combined with modern radiation treatment techniques, such as 3DCRT or IMRT, reduction of PTV margins in prostate cancer external beam radiotherapy [EBRT] reduces dose to nearby normal tissues and could potentially allow an increased radiation dose to the prostate. However, tight margins could lead to geographical misses due to daily prostate displacement. The purpose of this study was to compare 2 distinctly different image-guided verification methods for prostate alignment during daily radiotherapy. A prospective clinical trial was conducted whereas prostate displacements were measured in 40 patients undergoing daily EBRT for prostate cancer. Comparison was made between a two-dimensional trans-abdominal ultrasound-based system (BAT System, NOMOS, Pennsylvania) [BAT] and a three-dimensional trans-abdominal ultrasound-based system (RESTITU System, Resonant Medical, Montreal) [RES]. A total of 217 BAT and 217 RES displacements measurements were collected within a minute of each other with all patients in the supine position. For prostate alignment with the BAT, two nearly orthogonal 2D ultrasound images obtained immediately prior to treatment were compared to the position of the CT-designed treatment planning volumes (i.e., cross-modality calculation method, comparing ultrasound to CT data). The RES system compared 3D ultrasound images acquired immediately prior to the planning CT scan to those acquired immediately prior to the treatment (i.e., intra-modality calculation method, comparing ultrasound to ultrasound data). Since the RES system resides in the CT-simulation room as well, prostate displacements were also compared to those measured by CT scan, which is the gold standard since it is used for treatment planning. This comparison was done in 10 patients, who were rescanned 3 additional times, at bi-weekly intervals, during their treatment course. The prostate displacement between the planning CT and the subsequent CT scans was calculated with the AcQSim CT-Sim Software (Phillips Medical Systems, Massachusetts) and compared to the 3D-US data obtained just prior each of the CT scans. Analysis performed on the difference in the paired 217 BAT and RES prostate displacements shows a mean difference of 0.9 (95% C.I. 0.5, 1.3) mm in the lateral [LAT] direction (p < 0.0001), of 0.1 (95% C.I. -0.5, 0.7) mm in the anteroposterior [A/P] direction (p = 0.604), and 6.0 (95% C.I. 5.4, 6.6) mm in the superoinferior [S/I] direction (p < 0.0001). These trends in the difference results are similar to those determined by Langen et. al.1, who compared the BAT system and implanted radio-opaque markers. Analysis of the thirty CT-scan and RES measured prostate displacements shows mean values of 0.2 (95% C.I. -0.4, 0.8) mm in the LAT direction (p = 0.314), - 0.3 (95% C.I. -0.9, 0.3) mm in the A/P direction (p = 0.405), and 0.1 (95% C.I. -0.5, 0.7) mm in the S/I directions (p = 0.727). Our study indicates that a significant systematic difference exists between cross-modality (BAT) and intra-modality (RES) methods when assessing prostate alignment during daily EBRT. Since RES displacements are consistent with the CT displacements, a more accurate prostate alignment is obtained when the RES method is used, compared to the BAT method.

A Decoupling Technique for Efficient Timing Analysis of VLSI Interconnects With Dynamic Circuit Switching

In today's high-speed/high-density very large scale integrated (VLSI) circuit designs with coupled interconnect lines, signal transients are strongly correlated with the input switching patterns. Signal-delay variations due to the input-switching patterns may be more than /spl plusmn/50% of the delay of an isolated single line. Thus, blind static timing-analysis techniques without consideration of the detailed switching effects may not be accurate enough to meet tight timing margins for today's deep submicron (DSM)-based VLSI circuits. In this paper, the signal-transient responses of multicoupled interconnect lines due to various input-switching patterns are analyzed in terms of the effective capacitances and effective inductances. Thereby, the critical delay line of multicoupled interconnect lines is decoupled into an effective single-isolated line. With the proposed novel decoupling technique for multicoupled interconnect lines, the accurate dynamic delay of strongly coupled interconnect lines can be readily determined with physical layout information. For example, in switching patterns, the paper shows that the signal delays calculated by using the effective single-line models have excellent agreement with SPICE simulations using the generic coupled interconnect circuit models. That is, the accuracy for both RC-dominant lines and RLC lines is within 10% error (but often within 5% error). Thus, without any significant modification of existing IC computer-aided design frameworks, the technique can be directly as well as usefully employed for accurate timing verification of DSM-based VLSI designs.

Predicting respiratory motion for four-dimensional radiotherapy.

Adapting radiation delivery to respiratory motion is made possible through corrective action based on real-time feedback of target position during respiration. The advantage of this approach lies with its ability to allow tighter margins around the target while simultaneously following its motion. A significant hurdle to the successful implementation of real-time target-tracking-based radiation delivery is the existence of a finite time delay between the acquisition of target position and the mechanical response of the system to the change in position. Target motion during the time delay leads to a resultant lag in the system's response to a change in tumor position. Predicting target position in advance is one approach to ensure accurate delivery. The aim of this manuscript is to estimate the predictive ability of sinusoidal and adaptive filter-based prediction algorithms on multiple sessions of patient respiratory patterns. Respiratory motion information was obtained from recordings of diaphragm motion for five patients over 60 sessions. A prediction algorithm that employed both prediction models-the sinusoidal model and the adaptive filter model-was developed to estimate prediction accuracy over all the sessions. For each session, prediction error was computed for several time instants (response time) in the future (0-1.8 seconds at 0.2-second intervals), based on position data collected over several signal-history lengths (1-7 seconds at 1-second intervals). Based on patient data included in this study, the following observations are made. Qualitative comparison of predicted and actual position indicated a progressive increase in prediction error with an increase in response time. A signal-history length of 5 seconds was found to be the optimal signal history length for prediction using the sinusoidal model for all breathing training modalities. In terms of overall error in predicting respiratory motion, the adaptive filter model performed better than the sinusoidal model. With the adaptive filter, average prediction errors of less than 0.2 cm (1sigma) are possible for response times less than 0.4 seconds. In comparing prediction error with system latency error (no prediction), the adaptive filter model exhibited lesser prediction errors as compared to the sinusoidal model, especially for longer response time values (>0.4 seconds). At smaller response time values (<0.4 seconds), improvements in prediction error reduction are required for both predictive models in order to maximize gains in position accuracy due to prediction. Respiratory motion patterns are inherently complex in nature. While linear prediction-based prediction models perform satisfactorily for shorter response times, their prediction accuracy significantly deteriorates for longer response times. Successful implementation of real-time target-tracking-based radiotherapy requires response times less than 0.4 seconds or improved prediction algorithms.