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Role for proton beam irradiation in treatment of pediatric CNS malignancies.

The ability to vary the proton energy (depth of beam penetration) and modulate the dose distribution at the end of range permits delivery of an increased dose to the designated cancer-containing volume with a reduced dose to overlying normal brain tissue. The evolution of childhood CNS malignancy following therapy is reviewed to identify radiation response variables indicating where the proton dose distribution will improve the therapeutic ratio. The review documents that of the 1262 children expected to develop CNS malignancy in 1989, only 43% will survive 5 years. About 75% of those with medulloblastoma and over 90% with astrocytoma die from persistent (in-field) disease. When the patient has been treated with radiation, it is accepted that disease persistence indicates the cancer dose was insufficient. Potentially 536 children could show an improved incidence of local control and improved survival from an increased cancer dose available from proton irradiation. As the total dose and volume of brain irradiated is increased about 1800 cGy, brain dysfunction increases, producing a spectrum of functional and intellectual deficits which are age and volume related. About 900 irradiated patients would have fewer in-field histologic and functional changes if the dose to normal brain, or the volume of brain irradiated, is reduced by an improved dose distribution. A proton beam treatment plan, delivering a cancer dose of 7400 cGy, is simulated for a thalamic astrocytoma. The dose distribution of this plan is compared with an x-ray plan used to treat a patient, in which a dose of 5400 cGy was delivered to the astrocytoma. Comparative isodose distributions and dose-volume histograms indicate a decreased integral dose to normal brain and a decreased volume of normal brain irradiated, even as the cancer dose is boosted 2000 cGy with protons.

Brain Neoplasms↗

Re-irradiation of pituitary adenoma.

Fifteen patients initially irradiated for pituitary adenoma were subsequently treated with a second course of radiotherapy at the University of California at San Francisco between 1961 and 1989. The re-irradiation followed surgery in all but two cases. The median time to recurrence was 9 years (range 2-17) and median follow-up after the second course of radiotherapy was 10 years (range 1-30). The median initial radiation dose was 4084 cGy; that at recurrence was 4200 cGy. Local control has been maintained in 12 patients. One failed locally with a benign adenoma that was surgically salvaged. Two developed pituitary carcinomas which were poorly controlled. Of the patients who presented with visual abnormalities at the time of recurrence, 50% improved and the remainder stabilized after re-irradiation. There are no long-term visual complications. Hypopituitarism was present in nine patients prior to the second course of radiotherapy and developed in the remaining six patients after re-irradiation. Temporal lobe injury was seen in two patients. Careful analysis of each patient's pituitary and temporal lobe doses, intervals between treatments, treatment volume, neurets, relative decay factors, absolute decay factors, TDF and modified LQF values, and dose-volume relationships, revealed no correlation with complication or likelihood of local control. Repeat radiotherapy for recurrent pituitary adenoma with the doses used in these patients appears to carry acceptable risk with good local control.

Adenoma↗

The objective evaluation of alternative treatment plans. III: The quantitative analysis of dose volume histograms.

The computer program OSCAR evaluates dose-volume histograms in a consistent way for use in 3-dimensional treatment planning. Based on a dose prescription specified by a radiation oncologist, the technique provides a quantitative and easily understood visual analysis of a proposed dose distribution. Rapid, reliable, and consistent choices can be made between alternative treatment plans, and if necessary the results of OSCAR calculations can be used to guide the design of a plan that will be closer to the required prescription. The method is well suited to use in the definition of treatment protocols. The use of OSCAR is demonstrated by applying it to the evaluation of alternative volumetric treatment plans for ca lung. The results demonstrate the importance of using corrections for inhomogeneous tissue density in the calculation of 3-dimensional dose distributions.

Computer Graphics↗

Indications for and the significance of seminal vesicle irradiation during 3D conformal radiotherapy for localized prostate cancer.

PURPOSE: To evaluate the use of pretreatment prostate specific antigen, Gleason score, and clinical stage as predictors of the risk of seminal vesicle involvement in patients with clinically localized prostatic cancer, and to determine the impact of excluding the seminal vesicles on the dose received by surrounding normal tissues. METHODS AND MATERIALS: An empirically derived equation combining the preoperative prostate specific antigen and Gleason score was applied to 188 patients treated with radical prostatectomy, for whom pathologic evaluation of the seminal vesicles was available. High and low risk groups for seminal vesicle involvement were defined using this equation. The observed risks of seminal vesicle involvement was compared to the predicted risk using the preoperative prostate specific antigen, Gleason score or clinical stage alone or using the empirical equation. Dose-volume histograms for five patients treated using six-field conformal radiotherapy were compared including and excluding the seminal vesicles. RESULTS: Using the empirically derived equation, a low risk group of 109 patients was identified with a calculated risk of seminal vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the high risk group of 79 patients, which included all patients with a calculated risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk). Twenty percent of the rectal volume received on average above 86% of the total dose for the five plans which included the seminal vesicles compared to 68% for the five plans excluding the seminal vesicles. The doses to 40% of the rectal volume were 64% and 37% if the seminal vesicles were included and excluded, respectively. The dose to the bladder and femoral heads was also decreased but to a lesser extent. CONCLUSION: The empirical formula predicts risk of seminal vesicle involvement with a higher degree of significance for a larger number of patients than either Gleason score, clinical stage, or prostate specific antigen alone. Based on an analysis of our first 100 patients treated with definitive conformal therapy alone, approximately 47% of those patients could have been treated excluding the seminal vesicles. Excluding the seminal vesicles may allow us to go to a higher total dose with less rectal toxicity.

Humans↗

The tetrad and hexad: maximum beam separation as a starting point for noncoplanar 3D treatment planning: prostate cancer as a test case.

PURPOSE: In contrast to computer optimized three-dimensional (3D) treatment planning, we have used maximally separated, noncoplanar beams as the starting point for 3D treatment planning of prostate cancer to maximize the rate of dose fall off from the target volume and minimize dose to surrounding tissues. MATERIALS AND METHODS: A planar four-field plan, a planar six-field plan, a tetrad plan, and a hexad plan are analyzed using a 3D treatment planning system which is capable of displaying real-time 3D dose distributions within volume reconstructed data sets (VISTAnet--an extension of the virtual simulator). The tetrad plan is based on the methane molecule and the hexad plan has a minimum separation of 58 degrees on beam entrance. All fields are conformal. The irradiated volume equals the clinical target volume plus a 1 cm margin. Competing plans are compared using cumulative dose-volume histograms and normal tissue complication probabilities. RESULTS: The crossover point, the isodose surface that conforms more to the beams than the target, is introduced and described. The hexad and tetrad plans result in tighter dose distributions when compared to the planar plans with the same number of beams. The tetrad plan treats a volume less than or equal to the planar six-field plan at isodose surfaces above 18% except between 37% and 44% where the tetrad volume is slightly larger. As expected from integral dose considerations, the amount of normal tissue receiving some radiation increases, but the amount receiving clinically significant amounts of radiation decreases as the number of beams increase. The plan involving the largest number of noncoplanar beams results in the tightest isodose distribution. Analysis of rectal and bladder cumulative dose volume histograms does not reveal a clearly superior plan based on normal tissue complication probabilities. CONCLUSIONS: Using basic principles of solid geometry, maximally separated beams without significant overlap on exit or entrance can be designed which minimize clinically significant dose to surrounding tissues and tighten the isodose distribution around the target volume. The emphasis of this treatment plan optimization is geometric in contrast to methods using computer optimization or artificial intelligence.

Humans↗

Dose and volume effects on fibrosis after breast conservation therapy.

PURPOSE: To analyze factors involved in the development of fibrosis in the boost area after breast conservation therapy (BCT) in patients treated with continuous low dose rate iridium implants following 50 Gy whole breast irradiation. METHODS AND MATERIALS: Fibrosis was estimated by palpation in 404 patients by four physicians. The median follow-up (FUP) duration was 70 months (range 30-133 months). Original implant data were used for reconstruction and dose-volume calculations. The total dose of the external whole breast irradiation and iridium implants was expressed in Normalized Total Dose (NTD): the total dose given in fractions of 2 Gy, which is biologically equivalent to the actual dose given according to the linear-quadratic model, using an alpha/beta value of 2 Gy, and 1.5 h for the recovery half-life of sublethal damage repair. To identify predictors of fibrosis we used a proportional odds model in a polychotomous logistic regression analysis. RESULTS: Seven independent factors were identified that were related to the severity of fibrosis: age, duration of FUP, clinical T-size, photon beam energy, NTD level, implant volume, and adjuvant chemotherapy. From the proportional odds model, a volume exponent could be estimated (0.16 +/- 0.04) that enabled us to determine dose-effect relations for different volumes. A 10-fold higher risk of fibrosis was seen when the total dose was above 79 Gy as compared with doses lower than 70 Gy. A fourfold increase in risk of fibrosis was seen for each 100 cm3 increase in irradiated boost volume. The use of adjuvant chemotherapy resulted in a twofold increase in the risk of fibrosis (dose modifying factor approximately 1.08). The application of Co-60 beams had a similar effect. The relative odds for the other factors were smaller (1.4 for each 10 years of older age, and 1.2 for clinical T-size over 20 mm). The FUP-period had a nonlinear effect: relative odds 2.2 at 6 years, 3.6 at 7-8 years, and 2.8 at 9-11 years. The dose rate (mean 0.57, range 0.26-0.89 Gy/h) had no influence on the development of fibrosis and there was no correlation between dose rate and irradiated volume. CONCLUSIONS: To optimize cosmetic results after BCT, both the total dose and the irradiated volume should be kept as low as possible. Minimum effective dose levels still have to be established. The boost volume can be minimized by more conformal brachytherapy techniques and optimal localization. It may be worthwhile to take adjuvant chemotherapy into account in decisions on boost dose levels.

Adult↗

Expanding the use and effectiveness of dose-volume histograms for 3-D treatment planning. I: Integration of 3-D dose-display.

PURPOSE: A technique is presented for overcoming a major deficiency of histogram analysis in three-dimensional (3-D) radiotherapy treatment planning; the lack of spatial information. METHODS AND MATERIALS: In this technique, histogram data and anatomic images are displayed in a side-by-side fashion. The histogram curve is used as a guide to interactively probe the nature of the corresponding 3-D dose distribution. Regions of dose that contribute to a specific dose bin or range of bins are interactively highlighted on the anatomic display as a window-style cursor is positioned along the dose-axis of the histogram display. This dose range highlighting can be applied to two-dimensional (2-D) images and to 3-D views which contain anatomic surfaces, multimodality image data, and representations of radiation beams and beam modifiers. Additionally, as a range of histogram bins is specified, dose and volume statistics for the range are continually updated and displayed. RESULTS: The implementation of these techniques is presented and their use illustrated for a nonaxial three field treatment of a hepatic tumor. CONCLUSION: By integrating displays of 3-D doses and the corresponding histogram data, it is possible to recover the positional information inherently lost in the calculation of a histogram. Important questions such as the size and location of hot spots in normal tissues and cold spots within target volumes can be more easily uncovered, making the iterative improvement of treatment plans more efficient.

Humans↗

Preliminary results of a prospective trial using three dimensional radiotherapy for lung cancer.

PURPOSE: To evaluate the preliminary results of a prospective trial using three-dimensional (3D) treatment for lung cancer. METHODS AND MATERIALS: Seventy patients with inoperable Stage I through IIIB lung cancer were treated with three-dimensional thoracic irradiation with or without chemotherapy (35% received chemotherapy). Total prescribed dose to the tumor ranged from 60-74 Gy (uncorrected for lung density). All patients were evaluated for local control, survival, and development of pneumonitis. These parameters were evaluated in respect to and compared with three-dimensional parameters used in their treatment planning. RESULTS: With a minimum follow-up of 6 to 30 months, the 2-year cause-specific survival rate for Stages I and II was 90% and 53% for Stage III (no difference between Stages IIIA and IIIB). Patients with local tumor control had a better 2-year overall survival rate (47%) than those with local failure (31%). Volumetrically heterogeneously calculated doses were important to the accurate delineation of dose-volume coverage as there was a wide range of discrepancies between a homogeneously prescribed point dose calculation and the heterogeneously calculated volume coverage of that prescription. High-grade pneumonitis was correlated with the location of the tumor with lower lobe tumors having a much higher risk than those with upper lobe tumors. A critical volume effect and threshold dose were apparent in the development of high-grade pneumonitis. CONCLUSIONS: Three-dimensional therapy for lung cancer has been practically implemented at the Mallinckrodt Institute of Radiology and shows promising results in our preliminary analysis. The incidence of high-grade pneumonitis, however, warrants careful selection of patients for future dose escalation. Future dose escalation trials in lung cancer should be directed to volumes that limit the amount of elective nodal irradiation. However, the volume of necessary elective nodal irradiation remains unknown and should be studied prospectively. Dose escalation trials are indicated and may be facilitated by smaller target volumes.

Adenocarcinoma↗

Comparison of miniature multileaf collimation (MMLC) with circular collimation for stereotactic treatment.

PURPOSE: A prototype Miniature Multi-Leaf Collimator (MMLC) designed specifically for radiosurgery and small field radiotherapy has been fabricated and evaluated at the University of Texas M. D. Anderson Cancer Center (UTMDACC). This work demonstrates the advantages of a computer-controlled MMLC vs. conventional circular collimation for the treatment of an irregularly shaped target volume in the brain. METHODS AND MATERIALS: Two patient treatments were selected for this comparison from 38 intracranial tumors treated with radiosurgery at UTMDACC from 8/6/91 to 5/10/94. Target contours and critical structures defined for one of the patients was used to create a simulated target volume and critical structures in a spherical head phantom. Computer simulations were performed using traditional single isocenter treatment with a circular collimator for a set of six arcs. The same arc paths were used to compute the dose distribution for the MMLC and conformed beam geometries were defined using a three-dimensional (3D) treatment planning system with beam's eye view capabilities. Then, the calculated dose distribution for a single isocenter, conformal treatment was delivered to the spherical head phantom under static conditions by shaping the MMLC to conform the target volume shape projected as a function of couch rotation and gantry angle. Planar dose distributions through the target volume were measured using therapy verification film located in the phantom. The measurements were used to verify that the 3D treatment planning system was capable of simulating the MMLC technique. For the second patient with a peanut-shaped tumor, the 3D treatment planning calculations were used to compare dose distributions for the MMLC and for traditional single and multiple isocenter treatments using circular collimators. The resulting integral dose-volume histograms (DVHs) for the target volume, normal brain, and critical structures for the three treatment techniques were compared. RESULTS: (a) Analysis of the film dosimetry data exemplified the degree of conformation of the high-dose region to the target shape that is possible with a computer-controlled MMLC. (b) Comparison of measured and calculated dose distributions indicates that the 3D treatment planning system can simulate the MMLC treatment. (c) Comparison of DVHs from the single isocenter MMLC and circular collimator treatments shows similar coverage of the target volume with increased dose to the brain for circular collimation (4). Comparison of DVHs from the single isocenter MMLC with the multiple isocenter circular collimator treatment approach shows a more inhomogeneous dose distribution through the target volume and increased dose to the brain for the latter. CONCLUSION: Dosimetry data for single isocenter treatments using computer-controlled field shaping with a MMLC demonstrate the ability to conform the dose distribution to an irregularly shaped target volume. DVHs validated that the single isocenter MMLC treatment is preferable to both single and multiple isocenter, circular collimator treatment because it provides a more uniform dose distribution to an irregularly shaped target volume and reduces the dose to surrounding brain tissue for the example cases.

Adenocarcinoma↗

Proton beams in radiation therapy.

The rationale for study of proton radiation therapy is that, for some anatomic sites and tumors, the treatment volume is smaller; i.e., there is less irradiation of nontarget tissue while the target is included in three dimensions at each treatment session. As a result, the dose to the target can be raised. The consequence is that the tumor control probability improves and the frequency and severity of treatment-related morbidity decrease. These results come about from the physical fact that the proton range in tissue is finite; in comparison, absorption of photons is an exponential function and, hence, some dose is received for the full-beam path through the body. Accordingly, the dose deep to the target for proton treatments can be zero for each beam path. This situation provides a virtually certain means of improving the treatment outcome for selected categories of patients. Experience to date with proton radiation therapy has been quite limited. As of June 1991, the total number of proton radiation-treated patients was 11,763 from the various centers. Of that number, approximately 46% and 32% have been treated for small benign intracranial lesions (principally pituitary adenomas and arteriovenous malformations) and for tumors of the eye, respectively. Thus, only some 2500 patients have been treated for all other tumor types. The results from three centers and approximately 2800 patients with uveal melanoma are that the local control rate was 96% (for failures in-field, marginal, and in other parts of the eye). The local control results for chondrosarcomas and chordomas of the skull base are 91% and 65%, respectively. These percentages compare with some 35% achieved with conventional treatment. Experience with arteriovenous malformations indicates that control of bleeding and disappearance of the lesion are comparable to those achieved by other procedures. The developments from the proton therapy programs have contributed greatly to radiation treatment planning, e.g., the first three-dimensional treatment planning system put into regular clinical use (uveal melanoma), beam's eye view, digital-reconstructed radiograph, dose-volume histograms, and definitions of the uncertainty in dose around any defined point. The potential for clinical gains is high. In May 1991, the Proton Radiation Oncology Group was formed to design, supervise, and coordinate clinical trials and to assist in data analysis. The efficacy of proton radiation therapy will be compared with that of photon therapy of the very highest technology.

Arteriovenous Malformations↗

Alternating conformal neutron and photon irradiation for locally advanced adenocarcinoma of the prostate.

The substantial local failure rate for patients with locally advanced carcinoma of the prostate (LACaP) following photon irradiation, the association of local failure with a poor prognosis, and the promising results of mixed neutron/photon (40%/60%) radiotherapy supplied the rationale for this study. The purpose of this study was to evaluate the combined advantages of mixed neutron/photon (75%/25%) irradiation, 3D treatment planning, as well as fully conformal beam shaping capabilities in reducing the morbidity associated with neutron irradiation. The first 35 patients treated with this technique are the basis for this analysis. After CT stimulation and treatment planning, the normal tissue and target structures were entered into the 3D planning system. The neutron dose was delivered in 15 fractions at 1.0 Gy/fraction (NGy) to the prostate and seminal vesicles (PSV) and 0.6 NGy/fraction to the pelvic lymph nodes (LN). The photon dose was given in 10 fractions of 1.8 Gy each to both the PSV and LN volumes. Neutron and photon dose-volume histograms (DVHs) were generated in each patient for the prostate, seminal vesicles, lymph nodes, bladder, and rectum. The adequacy of the neutron and photon components of the treatment were compared with respect to target volume and normal tissue irradiation. Based on the DVH analysis, the prostate and seminal vesicles received the prescribed dose with both neutrons (99% +/- 2%) and photons (99% +/- 2%). There was no significant difference in the dose to the bladder and rectum for both the neutrons and photons. The acute treatment related reactions have been mild, with only one grade III bladder reaction. The 3D conformal technology utilized in this study has been shown to allow for the delivery of neutron irradiation with no increase in dose to the adjacent normal tissues compared with that achieved with conformal photon treatment. Further follow-up will reveal whether the dosimetric advantage demonstrated by this technique translates into an improved therapeutic ratio.

Adenocarcinoma↗

Results of re-irradiation of primary intracranial neoplasms with three-dimensional conformal therapy.

We evaluated the potential of three-dimensional conformal therapy for re-irradiation of selected intracranial neoplasms and reviewed the retreatment of 20 patients at the University of Michigan between May 1988 and August 1991. All patients had previously undergone a full course of external beam radiotherapy (RT) to a median dose of 5,940 cGy (range 5,100-6,500 cGy), including five whole brain treatments. All recurrences were unsuitable for brachytherapy or radiosurgery. Various histologies were retreated, including 14 high-grade gliomas. Median time to re-irradiation was 38 months (range 9 months to 19 years, 6 months). RT was delivered with complex plans designed using fully integrated computed tomography/magnetic resonance imaging (CT/ MRI) tumor volume information, and regions of previous parenchymal treatment were avoided if possible. Composite (initial+retreatment) dose-volume histograms (DVH) of dose to nontarget brain allowed comparison of alternative plans to select beam orientations which minimized normal brain irradiation. Mean target dose of re-irradiation was 3,600 cGy (range 3,060-5,940 cGy). Total cumulative dose ranged from 8,060 to 11,940 cGy. Median survival was 9 months, and 1-year actuarial survival was 26%. After retreatment, 8 of 12 patients (67%) had steroid dose decrement and neurologic improvement at 4-48 months (median duration 14 months). Radiographic regression or stabilization of disease was noted in 11 of 16 patients (68%). Re-irradiation with highly conformal three-dimensional planning provides frequent clinical improvement with acceptable morbidity and should be considered in selected patients with recurrent intracranial neoplasms.

Actuarial Analysis↗

3-D dose-volume compensation using nonlinear least-squares regression technique.

A method for external beam dose-volume optimization is presented. The Gauss-Marquardt nonlinear least-squares regression technique is applied to compensator design and determination. The dose distribution (uniform or otherwise) desired throughout a volume is specified. Compensators optimized to produce the necessary variation of beam intensity across the surface of each beam are simultaneously determined for all the beams. Solutions for homogeneous dose, homogeneous target dose, and restricted dose to exterior target volume structures, and inhomogeneous target dose cases are presented. Dependence of the results on the number of parameters as well as the role of degree of desirability weighting is explained and illustrated via examples. Discussion of the significance and limitations of this optimization method is also presented.

Humans↗

Dose-volume histogram computations for small intracranial volumes.

A sampling formalism is presented to accurately compute the absolute volumes and integral dose-volume histograms of small volumes treated in stereotactic radiosurgery. The presence of small volumes and sharp dose gradients places special constraints on the computational formalism and the accuracy required to compute the dose-volume relationships. We use a spatially nonuniform random sampling method to allow an efficient and accurate computation of the dose-volume histograms for an arbitrary number of volumes. The computation of absolute volume vs dose allows intercomparison of dose delivered to target and dose-critical volumes and allows a quantitative trade-off analysis often critical to an optimal treatment of the lesion.

Algorithms↗

Dose-volume distributions: a new approach to dose-volume histograms in three-dimensional treatment planning.

A new approach to calculating and displaying dose-volume relationships in 3D radiation therapy is presented. We have developed a concept of a dose-volume distribution (DVD) and its corresponding differential dose-volume distribution (DDVD), based on organization of the data in the volume rather than in the dose domain. The new concepts make full use of the information that can be obtained from the dose calculation points and the sampling pattern and are designed to overcome shortcomings of the classical concepts of dose-volume histograms (DVH) and differential dose-volume histograms (DDVH). The new concepts can be applied to any number of dose calculation points, but they are especially advantageous when a small number of points is used. DVDs are particularly well suited to pseudo- and quasi-random sampling of dose distributions. We have developed an error analysis for DVDs and DDVDs in the case of pseudorandom sampling. We also describe an adaptive technique for minimizing the amount of data needed for purposes of display.

Biophysical Phenomena↗

Dose-surface histograms as treatment planning tool for prostate conformal therapy.

Dose-surface histograms are studied and compared with dose-volume histograms, as an evaluation tool for prostate treatment planning. For thin walled hollow organs, such as the rectum and bladder, the surface area irradiated is a more appropriate measure of the biological effect than the full volume. It is also more accurate and efficient to define the surface for a hollow structure and compute the surface area histograms. Application of the dose-surface histograms provide new insights into prostate treatment planning. A simple idealized geometry model demonstrates that the percentage surface area intersected by the geometric beam edge differs from the percentage volume intersected. For a group of prostate patients, it is shown that the dose-surface histograms yield substantially different results from the dose-volume histograms in ranking four-, six-, and, eight-field treatment plans and in calculating the fraction of the rectum irradiated to high dose. The difference in terms of surface area between these plans in the high-dose region is usually less than that in terms of the volume, and a reverse of plan ranking order can consequently occur. The percentage of organ surface irradiated to high dose is typically greater than the percentage volume by 5% to 10%. The use of the dose-surface histograms in analysis of organ motion and/or patient setup uncertainty, and analysis of rectal complications, is also discussed.

Biophysical Phenomena↗

Reporting and analyzing dose distributions: a concept of equivalent uniform dose.

Modern treatment planning systems for three-dimensional treatment planning provide three-dimensionally accurate dose distributions for each individual patient. These data open up new possibilities for more precise reporting and analysis of doses actually delivered to irradiated organs and volumes of interest. A new method of summarizing and reporting inhomogeneous dose distributions is reported here. The concept of equivalent uniform dose (EUD) assumes that any two dose distributions are equivalent if they cause the same radiobiological effect. In this paper the EUD concept for tumors is presented, for which the probability of local control is assumed to be determined by the expected number of surviving clonogens, according to Poisson statistics. The EUD can be calculated directly from the dose calculation points or, from the corresponding dose-volume distributions (histograms). The fraction of clonogens surviving a dose of 2 Gy (SF2) is chosen to be the primary operational parameter characterizing radiosensitivity of clonogens. The application of the EUD concept is demonstrated on a clinical dataset. The causes of flattening of the observed dose-response curves become apparent since the EUD concept reveals the finer structure of the analyzed group of patients in respect to the irradiated volumes and doses actually received. Extensions of the basic EUD concept to include nonuniform density of clonogens, dose per fraction effects, repopulation of clonogens, and inhomogeneity of patient population are discussed and compared with the basic formula.

Cell Division↗

[The dose-volume factor in radiotherapy. Significance of the focal or tumor volume for the evaluation of radiotherapeutic effect].

The absorbed energy dose, in dependence on the irradiated tissue volume or tumor volume (dose-volume-relations) has great significance for the valuation of radiation injuries and of the prognosis of the disease. The present paper includes an analysis, formal demonstrations and interpretation of these relations. Clinical observations and radiobiological experiments in literature were the basis of the present investigation. The assessment is kept simple, the models derived from it interprete well the clinical findings. Through these models, radiobiological findings and clinical experimental principles are connected. This results in a clear conception of the future development of irradiation planning, and the application technique of radiation. The range of validity of the cited models includes the treated volumes usual in radiotherapy. An extrapolation to the cellulary area or to the whole body may only be made with great reservations.

Humans↗