Leon C. Myrianthopoulos

Optimization of radical radiotherapy with beam's eye view techniques for non-small cell lung cancer

The presence of vital and sensitive organs such as the spinal cord, heart, and lungs makes curative radiotherapy of non-small cell lung cancer difficult to implement and necessitates use of oblique portals. Defining the target volumes in oblique portals is very difficult. We now show, for non-small cell lung cancer, how beams eye view-based radiotherapy can be used for accurate delineation of treatment volumes and for avoidance of real or dosimetric geographic misses. Furthermore, the beams eye view-based method enables one to project accurately a 2-dimensional image of 3-dimensional disease extension, especially in oblique fields, thus facilitating the design of accurate customized blocking and avoiding inadvertent blocking of the tumor or unnecessary irradiation of normal tissues. Beams eye view volumetric analysis is helpful for devising a customized treatment plan for each patient. Such customization may minimize local failure, which is one cause of poor results of radiotherapy in this site. Beams eye view-based radiotherapy has the potential of improving local control and hence may improve the survival of patients with non-small-cell lung cancer.

Randomized neutron dose searching study for malignant gliomas of the brain: Results of an RTOG study

From September 1980 through January 1985, the Radiation Therapy Oncology Group (RTOG) conducted a randomized, dose-searching study testing the efficacy of a concomitant neutron boost along with whole brain photon irradiation in the treatment of malignant gliomas of the brain. Patients had to have biopsy-proven, supratentorial, anaplastic astrocytoma or glioblastoma multiforme (Nelson schema) to be eligible for the study. The whole brain photon irradiation was given at 1.5 Gy per treatment, 5 days-a-week to a total dose of 45 Gy. Two days-a-week the patients were to receive neutron boost irradiation to the tumor volume as determined on CT scans. The neutron irradiation was to be given prior to and within 3 hours of the photon irradiation on that day. The rationale for this particular treatment regime is discussed. A total of 190 evaluable patients were randomized among 6 different neutron dose levels: 3.6, 4.2, 4.8, 5.2, 5.6 and 6.0 Gyn gamma. There was no difference in overall survival among the 6 different dose levels, but for patients having less aggressive tumor histology (anaplastic astrocytoma), there was a suggestion that patients on the higher dose levels had poorer overall survival than patients on the lower dose levels and also did worse than historical photon controls. Important prognostic factors were identified using a Cox stepwise regression analysis. Tumor histology, Karnofsky performance status, and patient age were found to be related to survival while extent of surgery and neutron dose had no significant impact. Autopsies were performed on 35 patients and the results correlated with the actual neutron dose as determined by central-axis isodose calculations. At all dose levels there were some patients with both radiation damage to normal brain tissue and evidence of viable tumor. No evidence was found for a therapeutic window using this particular treatment regimen.

In vivo and phantom measurements of the secondary photon and neutron doses for prostate patients undergoing 18 MV IMRT

For intensity modulated radiation therapy (IMRT) treatments 6MV photons are typically used, however, for deep seated tumors in the pelvic region, higher photon energies are increasingly being employed. IMRT treatments require more monitor units (MU) to deliver the same dose as conformal treatments, causing increased secondary radiation to tissues outside the treated area from leakage and scatter, as well as a possible increase in the neutron dose from photon interactions in the machine head. Here we provide in vivo patient and phantom measurements of the secondary out-of-field photon radiation and the neutron dose equivalent for 18MV IMRT treatments. The patients were treated for prostate cancer with 18MV IMRT at institutions using different therapy machines and treatment planning systems. Phantom exposures at the different facilities were used to compare the secondary photon and neutron dose equivalent between typical IMRT delivered treatment plans with a six field three-dimensional conformal radiotherapy (3DCRT) plan. For the in vivo measurements LiF thermoluminescent detectors (TLDs) and Al2O3 detectors using optically stimulated radiation were used to obtain the photon dose and CR-39 track etch detectors were used to obtain the neutron dose equivalent. For the phantom measurements a Bonner sphere (25.4cm diameter) containing two types of TLDs (TLD-600 and TLD-700) having different thermal neutron sensitivities were used to obtain the out-of-field neutron dose equivalent. Our results showed that for patients treated with 18MV IMRT the photon dose equivalent is greater than the neutron dose equivalent measured outside the treatment field and the neutron dose equivalent normalized to the prescription dose varied from 2 to 6mSv∕Gy among the therapy machines. The Bonner sphere results showed that the ratio of neutron equivalent doses for the 18MV IMRT and 3DCRT prostate treatments scaled as the ratio of delivered MUs. We also observed differences in the measured neutron dose equivalent among the three therapy machines for both the in vivo and phantom exposures.

An updated dose-response analysis in Hodgkin's disease

Although radiotherapy cures a very high percentage of early stage patients with Hodgkins disease (HD), there is a controversial dichotomy in the dose recommendations believed necessary to achieve greater than 95% local control: Whereas one school of thought is to administer 40-44 Gy, other reports claim equal results with about 36 Gy. It is also not clear what doses are required for various tumor cell burdens. The original recommendation of 40-44 Gy was derived from a retrospective analysis of in-field control of disease from mostly kilovoltage data three decades ago. However, there have been many advances in the evaluation of the extent of the disease and in the practice of radiotherapy since the 1960s. Many more dose-control studies have been published in recent years, necessitating a revisit to the dose-response question in HD. Here we have compiled the dose-control data from the 60s to the 90s and analyzed the original and the updated data with the same statistical method to see any differences. We also have performed similar analysis of dose-control information for subclinical disease, less than 6 cm and greater than 6 cm disease. Whereas original analysis (1040 sites at risk) suggested 98% in-field control with 44 Gy, our re-analysis including modern megavoltage data (4117 sites at risk) shows that similar in-field control rates could be achieved with 37.5 Gy. With megavoltage radiotherapy, the doses required for 98% in-field control for subclinical disease and disease of less than 6 cm and greater than 6 cm are, 32.4 Gy (1426 sites at risk), 36.9 Gy (1005 sites at risk) and 37.4 Gy (98 sites at risk), respectively. The results of current updated analysis will provide in-field disease control probabilities for different disease burdens and can serve as a guide in deciding dose prescriptions for practicing radiation oncologists.

Beams eye view-based photon radiotherapy I

Geographic miss, dosimetric miss (underdosing), and proximity of the tumor to sensitive normal tissues are some of the causes of inadequate radiation dose delivery; this is one of many causes of failure after radiotherapy. In the past decade, computerized tomography (CT)-based treatment planning has helped to overcome some of these problems. Beams eye view (BEV)-based radiotherapy planning is an improvement over CT-based treatment planning that may further increase the therapeutic ratio. Since January 1988, we have treated 198 patients with BEV-based photon radiotherapy. About 40% of our patients treated with radical radiotherapy undergo BEV-based treatment, and about 70% of patients who undergo planning CT in the treatment position receive BEV-based radiotherapy. Our findings are as follows: (a) routine use of BEV-based RT (BEVRT) is possible in a busy radiation oncology department; (b) BEVRT improves geometric coverage of tumors; (c) BEVRT is extremely useful in the design of oblique portals; (d) time commitments for various members of the RT treatment-planning team are reasonable; (e) BEVRT helps individualize RT technique; (f) preliminary data suggest decreased acute toxicity with the use of BEVRT for prostate cancer patients. Whether these advantages will help to improve the outcome (i.e., improve local control and survival) and/or decrease the long-term toxicity is not yet known.

The use of beam's eye view volumetrics in the selection of non-coplanar radiation portals

In 3-dimensional treatment planning, beams eye view (BEV) is used as an interactive tool to define portal entry angles that exclude critical structures while fully encompassing the target volume. With beams eye view volumetrics (BEV volumetrics), the volume of intersected normal tissues is also calculated and is used as a quantitative tool to choose portal orientations that minimize normal tissue volumes irradiated. The axial beam entry angle and a polar angle (relative to the patient longitudinal axis) are specified to define the central axis orientation. Using BEV volumetrics, we have studied the quantities of normal tissues irradiated when treating tumors in the abdomen, thorax, and pelvis. The reduction of normal tissue irradiated is a strong function of site and patient-specific tumor size and location. Volumetrics combined with BEV is found to be useful in treatment planning because it (a) provides quantitative information needed in rationally choosing portal entry angles, (b) provides a near interactive speed approach to understanding the relative merits of different multiple field plans, and (c) compliments the information provided by the more time-consuming generation of dose volume histograms.

Beam's eye view volumetrics: An aid in rapid treatment plan development and evaluation

A well-designed treatment plan fully irradiates the target to the prescribed dose while minimizing radiation to adjacent critical structures. Beams eye view is an important component of treatment planning systems because it provides the operator with tools needed to achieve this goal. Through interactive manipulation of displays, the planner uses beams eye view to adequately cover the target volume while geometrically avoiding certain critical, normal structures. A factor not considered in current beams eye view programs is the fractional volume of each structure irradiated given a specified beam direction. We have incorporated a rapid volume calculation capability in our beams eye view program, and have applied it to provide a quantitative aid to treatment planning development and evaluation. Treatment planning of lung tumors has been studied using this tool. Volumes of lung and spinal cord treated as a function of portal angle may be calculated much more rapidly than dose volume histograms and yet provide quantitative indices which follow the trends of dose volume histograms as a function of field angle. Plots of normal tissue volume irradiated as a function of field angle identify the optimal angle to minimize irradiated volume of a structure at a glance. For multiple field plans, a bitmap approach identifies areas treated by various combinations of beams. Volumetrics combined with beams eye view are useful in treatment planning because they (a) provide quantitative information needed in choosing and optimizing portal entry angle (b) provide an interactive approach to understanding the relative merits of different multiple field plans and (c) complement the information provided by the more time consuming generation of dose volume histograms. The clinical application of this tool in treatment planning is presented.

Comparison of CT-based treatment planning and retrograde urethrography in determining the prostatic apex at simulation

In 20 consecutive patients who underwent treatment planning, localization of the prostatic apex with CT-based techniques at simulation was compared to location of the apex as defined by retrograde urethrography. In addition, the location of the urethrogram-defined prostatic apex was compared with the bottom of the ischial tuberosities, which is often recommended as the inferior margin of the field. In 15% of the patients there was agreement between the CT-defined apex and the urethrogram-defined apex; in 85% there was discordance. In a majority of patients with discordance, the urethrogram apex was located caudad to the CT-defined apex (71%) with a median difference of .65 cm. In 29% of the patients the urethrogram apex was located superior to the CT-defined apex. Overall, 75% of the patients had discordance between the urethrogram apex and the CT apex of 0.5 cm or greater; 30% had an absolute difference of 1.0 cm or greater. Comparing the location of the prostatic apex with the bottom of the ischial tuberosities revealed that in 15% of the patients the apex was 1.0 cm or less from the bottom of the tuberosities and in 45% it was less than 1.5 cm. This would place the apex of the prostate in the penumbra region of the field and risk undertreatment of the prostate if the bottom of the ischial tuberosities was the inferior margin of the field. Measuring the location of the prostatic apex from the top of the symphysis pubis revealed that a distance of 4.9 cm encompassed the apex in all 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of treatment volumes from CT and MRI in high-grade gliomas: Implications for radiotherapy

Long-term survival of patients with high-grade gliomas remains extremely poor. The main reason for such an outcome is local failure, or recurrence, after surgery and/or radiotherapy. Higher doses of radiation may result in decreased local failure rates provided that the location (and extent) of gross tumor and microscopic disease can be defined accurately. The abnormalities appearing in images from diagnostic modalities, such as CT and MRI, are being used as a starting point and as a guide for the clinical definition of tumor and its extensions. However, some recent studies on two-dimensional specimens, correlating histopathological findings to CT and MRI images, showed that the resulting definition of tumor cell extensions was unsatisfactory, different, and in need of ample margins. We carried out a retrospective analysis to compare the target volumes that would have been defined by CT, T2-weighted MRI, and T1-weighted postgadolinium MRI images of the same individual and to explore the implications of the resulting volume definitions for radiotherapy. The results of our limited study, based on the margins used, indicate that the CT-defined target volume is consistently larger than that from either of the two MRI modalities and suggest that noncoplanar approaches for its treatment and other local approaches for tumor boost should be considered. We conclude that until more definitive histopathological guidelines correlated to image features have been formulated and agreed upon, one should try to make full use of all available diagnostic information in order to minimize the possibility of geographical miss of target extensions.

Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis

In this work we review the dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to the normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented. The technique involves moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare the dose to normal structures within the spinal field. Our results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. In the case of bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons.