Quality of life in childhood epilepsy: what is the level of agreement between youth and their parents?

Children and parents evaluate the child's quality of life (QOL) from their own perspectives; therefore, responses may differ, especially in abstract domains. We examined differences between self- and proxy-reported QOL of children with epilepsy. Children with active epilepsy (N=375) and their parents (N=378) separately completed the CHEQOL-25, a condition-specific QOL measure. The intraclass correlation coefficient was used to determine interrater agreement. Concordance on the Total CHEQOL-25 was 0.45 (P<0.01). Discrepancies were greatest for the subscales of Secrecy (0.24, P<0.01) and Present Concerns (0.32, P<0.01). School placement correlated with discrepancy in the Intrapersonal/Emotional subscale (r=0.19, P<0.05), and the child's age at testing correlated with discrepancy of the Total measure (r=0.15, P<0.01). This study demonstrates that parent perspectives alone are insufficient to measure their child's QOL. The CHEQOL-25 is a practical tool, with complementary parent and child versions, which can be used to determine health-related quality of life in children with epilepsy.

Peripheral dose in ocular treatments with CyberKnife and Gamma Knife radiosurgery compared to proton radiotherapy.

Peripheral radiation can have deleterious effects on normal tissues throughout the body, including secondary cancer induction and cataractogenesis. The aim of this study is to evaluate the peripheral dose received by various regions of the body after ocular treatment delivered with the Model C Gamma Knife, proton radiotherapy with a dedicated ocular beam employing no passive-scattering system, or a CyberKnife unit before and after supplemental shielding was introduced. TLDs were used for stray gamma and x-ray dosimetry, whereas CR-39 dosimeters were used to measure neutron contamination in the proton experiments. Doses to the contralateral eye, neck, thorax and abdomen were measured on our anthropomorphic phantom for a 56 Gy treatment to a 588 mm(3) posterior ocular lesion. Gamma Knife (without collimator blocking) delivered the highest dose in the contralateral eye, with 402-2380 mSv, as compared with 118-234 mSv for CyberKnife pre-shielding, 46-255 mSv for CyberKnife post-shielding and 9-12 mSv for proton radiotherapy. Gamma Knife and post-shielding CyberKnife delivered comparable doses proximal to the treatment site, with 190 versus 196 mSv at the thyroid, whereas protons doses at these locations were less than 10 mSv. Gamma Knife doses decreased dramatically with distance from the treatment site, delivering only 13 mSv at the lower pelvis, comparable to the proton result of 4 to 7 mSv in this region. In contrast, CyberKnife delivered between 117 and 132 mSv to the lower pelvis. In conclusion, for ocular melanoma treatments, a proton beam employing no double scattering system delivers the lowest peripheral doses proximally to the contralateral eye and thyroid when compared to radiosurgery with the Model C Gamma Knife or CyberKnife. At distal locations in the pelvis, peripheral doses delivered with proton and Gamma Knife are of an order of magnitude smaller than those delivered with CyberKnife.

New technologies in the radiotherapy clinic.

What are the limitations to the accuracy of our current technologies in radiation oncology? The immobilization of the patient, definition of the target, motion of the target and localization of the target are the major concerns that must be addressed. Current approaches to meet these needs have brought new technical systems with greater precision and new clinical procedures with higher expectations of practice. This text offers discussions on these issues, including advances in intensity-modulated radiotherapy planning, clinical target definition for the major tumor sites, management of organ motion, target localization and image guidance systems, and the expanding applications of high-precision treatment with stereotactic body radiotherapy.

Comparison of three-dimensional conformal radiation therapy and intensity-modulated radiation therapy systems.

The use of three-dimensional conformal radiation therapy (3DCRT) has now become common practice in radiation oncology departments around the world. Using beam's eye viewing of volumes defined on a treatment planning computed tomography scan, beam directions and beam shapes can be selected to conform to the shape of the projected target and minimize dose to critical normal structures. Intensity-modulated radiation therapy (IMRT) can yield dose distributions that conform closely to the three-dimensional shape of the target volume while still minimizing dose to normal structures by allowing the beam intensity to vary across those shaped fields. Predicted dose distributions for patients with tumors of the prostate, nasopharynx, and paraspinal region are compared between plans made with 3DCRT programs and those with inverse-planned IMRT programs. The IMRT plans are calculated for either static or dynamic beam delivery methods using multileaf collimators. Results of these comparisons indicate that IMRT can yield significantly better dose distributions in some situations at the expense of additional time and resources. New technologies are being developed that should significantly reduce the time needed to plan, implement, and verify these treatments. Current research should help define the future role of IMRT in clinical practice.

The "critical volume tolerance method" for estimating the limits of dose escalation during three-dimensional conformal radiotherapy for prostate cancer.

PURPOSE: To describe the "Critical Volume Tolerance" (CVT) method for defining normal tissue tolerance during 3D-based dose escalation studies for prostate cancer. METHODS AND MATERIALS: The CVT method predicts the tolerance to radiation for "in series"-type functional units based on the assumption that tolerance depends on a critical threshold "low-volume high-dose region." The data used for describing this model were generated from 3D analysis of randomly selected patients with prostate cancer. Commonly used coplanar four-and six-field conformal (SFC) techniques were chosen as the comparison techniques. For purposes of comparison, rectal tolerance was assumed to be reached following whole pelvic irradiation using a four-field box technique to 50 Gy, followed by a conedown boost to 70 Gy using bilateral 9 x 9 cm 120 degree arcs as popularized by investigators from Stanford University (SUH). RESULTS: Based on the average dose volume histograms for the patients studied, the maximum safe increase in dose for the SFC technique compared to the SUH technique, would be 10% if 30% of the rectal volume was the critical dose limiting volume (CVT = 30%), 5% if the CVT = 10%, or greater than 20% if the CVT = 40%. Commonly used four-field conformal techniques would not be expected to allow significant escalation of the dose without increasing the risk of complications. CONCLUSIONS: The CVT method is relatively simple, and data generated based on it can be used to support normal tissue complication probability equations. The CVT method can be verified or modified as partial tolerance data become available. Based on the CVT model, sophisticated treatment techniques should allow a modest increase in the total dose of radiation delivered to the prostate without an increase in late complications.

Comparison of radiosurgery treatment modalities based on physical dose distributions.

PURPOSE: As a means of selecting the optimal stereotactic radiosurgery (SRS) treatment modality, a comparison of physical dose distributions to defined targets and nontarget brain tissue has been made for a group of test cases selected to represent a range of treatment-planning situations from small, nearly spherical volumes to large irregular volumes. METHODS AND MATERIALS: Plans were developed for each case using photon beams from the Leksell Gamma Unit (LGU), multiarc bremsstrahlung photon beams from a linear accelerator (linac) and proton beams, with the objective of encompassing the target as closely as possible with the prescription isodose line, and minimizing dosage to normal tissue within the bounds of standard clinical practice. Dose-volume histograms (DVHs) were calculated for target and for nontarget brain tissue and compared for the various modalities. RESULTS: In general, protons delivered less dosage to normal brain than other modalities for large and peripheral lesions and LGU plans were more successful at conforming to highly irregular shapes than conventional linac plans. CONCLUSIONS: Differences were observed to depend on treatment modality, target characteristics (shape, size and location), and the amount of effort expended on treatment planning and the time allotted for treatment implementation.

Comparison of radiosurgery treatment modalities based on complication and control probabilities.

PURPOSE: The relative efficacy of Gamma Knife, Linac, and Proton treatment modalities for stereotactic radiosurgery (SRS) was investigated on the basis of normal tissue complication probability (NTCP) and tumor control probability (TCP), calculated for representative test cases. METHODS AND MATERIALS: Five radiosurgery patient cases were selected to cover a range of treatment-planning situations from small spherical volumes to large irregular volumes. A target volume consisting of contours drawn on CT transverse slices was prepared for each case. Plans were developed using the three treatment modalities for each case, with the objective of encompassing the target as closely as possible with a prescription isodose line and minimizing dose to normal tissue, within the constraints of current clinical practice. Dose-volume histograms (DVH) were calculated for the target and for normal tissue, and these histograms were used to calculate NTCP and TCP values for each plan. RESULTS AND CONCLUSIONS: Differences in NTCP and TCP values were found to depend on treatment modality, size, shape, and location of the target, the amount of effort devoted to treatment planning, and the complexity of the plan.

Static field intensity modulation to treat a dominant intra-prostatic lesion to 90 Gy compared to seven field 3-dimensional radiotherapy.

PURPOSE/OBJECTIVE: Recent studies supported by histopathological correlation suggest that the combined use of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) allows differentiation of normal and carcinomatous prostate. The goal of this study was to use static field intensity modulated three-dimensional conformal radiotherapy (SF-IMRT) to treat the entire prostate to a total dose of >70 Gy, while concurrently treating a dominant intraprostatic lesion (DIL) defined by MRI+MRS to 90 Gy while not exceeding normal tissue tolerances. MATERIALS AND METHODS: For the example chosen, the DIL consisted of a large portion of the peripheral zone of the left lobe of the prostate. University of Michigan (UM-PLAN) three-dimensional treatment planning software was used to design a partially shielded 7 field conformal isodose plan that would treat the entire prostate to >70 Gy at 1.8 Gy per day (80% isodose line), while concurrently treating the DIL to 2.25 Gy per day for a total dose of 90 Gy. Dose volume histograms (DVH) were used to compare the rectal doses to rectum and other adjacent normal tissues using these two techniques. RESULTS: SF-IMRT as described, allowed a total dose of 90 Gy to encompass the DIL, while the rectal dose was slightly lower than that using the standard 7 field technique to the prostate alone. For example, the dose to 30 cm3 of the rectum was 40 Gy using SF-IMRT and 48 Gy for the standard 7 field technique. Because of differences in the dose per fraction the biologic advantages of the SF-IMRT technique are likely to be even greater. CONCLUSIONS: This study demonstrates the feasibility of using SF-IMRT to treat a DIL involving a single lobe of the prostate, as defined by MRI/MRS, to 90 Gy, while simultaneously treating the prostate to >70 Gy without increasing the dose to surrounding normal tissues. A similar approach could be used to treat multifocal disease. This method of treatment is an alternative to dynamic intensity modulation. It is less expensive, and can be adapted to any radiation therapy department without the use of an inverse treatment planning programs.

A dosimetric comparison of fan-beam intensity modulated radiotherapy with Gamma Knife stereotactic radiosurgery for treating intermediate intracranial lesions.

PURPOSE: To compare and evaluate treatment plans for the fan-beam intensity modulated radiotherapy and the Gamma Knife radiosurgery for treating medium-size intracranial lesions (range 4-25 cm3). METHODS AND MATERIALS: Treatment plans were developed for the Leksell Gamma Knife and a fan-beam inverse treatment planning system for intensity modulated radiotherapy. Treatment plan comparisons were carried out using dose-volume histogram (DVH), tissue-volume ratio (TVR), and maximum dose to the prescription dose (MDPD) ratio. The study was carried out for both simulated targets and clinical targets with irregular shapes and at different locations. RESULTS: The MDPD ratio was significantly greater for the Gamma Knife plans than for the fan-beam IMRT plans. The Gamma Knife plans produced equivalent TVR values to the fan-beam IMRT plans. Based on the DVH comparison, the fan-beam IMRT delivered significantly more dose to the normal brain tissue than the Gamma Knife. The results of the comparison were found to be insensitive to the target locations. CONCLUSION: The Gamma Knife is better than the fan-beam IMRT in sparing normal brain tissue while producing equivalent tumor dose conformity for treating medium-size intracranial lesions. However, the target dose homogeneity is significantly better for the fan-beam IMRT than for the Gamma Knife.

Forward or inversely planned segmental multileaf collimator IMRT and sequential tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer to 90 Gy.

PURPOSE: To investigate the technical feasibility of using forward or inversely planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple dominant intraprostatic lesions within the prostate gland while delivering a dose of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with one dominant intraprostatic lesion located at the left base and a second dominant intraprostatic lesion at the right apex of the prostate was planned using three different intensity modulation techniques. Two plans were generated with inverse treatment planning, using either SMLC or ST with a special multivane collimator. The third plan also employed SMLC but was generated using forward planning. All three plans were compared based on dose-volume histograms, isodose distributions, and doses to sensitive normal structures. RESULTS: All three plans meet and exceed the desired dose constraints, limiting doses to the rectum and bladder to an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques, it is technically feasible to concurrently treat multiple selected high-risk regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while keeping the doses to the rectum and the bladder significantly lower than those associated with a Grade 2 complication rate of 10%.

Potential for improvement in radiation therapy.

A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage IB), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned.

Precise positioning of patients for radiation therapy.

We have developed a number of immobilization schemes which permit precise daily positioning of patients for radiation therapy. Pretreatment and post-treatment radiographs have been taken with the patient in the treatment position and analyzed to determine the amount of intratreatment movement. Studies of patients in the supine, seated and decubitus positions indicate mean movements of less than 1 mm with a standard deviation of less than 1mm. Patients immobilized in the seated position with a bite block and a mask have a mean movement of about 0.5 mm +/- 0.3 mm (s.d.), and patients immobilized in the supine position with their necks hyperextended for submental therapy evidence a mean movement of about 1.4 mm +/- 0.9 mm (s.d.). With the exception of those used for the decubitus position, the immobilization devices are simply fabricated out of thermoplastic casting materials readily available from orthopedic supply houses. A study of day-to-day reproducibility of patient position using laser alignment and pretreatment radiographs for final verification of position indicates that the initial laser alignment can be used to position a patient within 2.2 mm +/- 1.4 mm (s.d.) of the intended position. These results indicate that rigid immobilization devices can improve the precision of radiotherapy, which would be advantageous with respect to both tumor and normal tissue coverage in certain situations.

Defining treatment margins for six field conformal irradiation of localized prostate cancer.

PURPOSE: To define the "ideal margins" to be used for the delivery of six-field conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For a typical patient, 3-D based 6-field conformal treatment plans were generated using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step-wise fashion the minimum margins required to encompass the gross tumor volume within the 90% isodose shell were identified. Additional margins were then added to account for extracapsular penetration, setup and patients movement error as well as for organ movement. Assumptions about the relative tolerance of surrounding normal tissues were also incorporated into the final decisions regarding margins. RESULTS: For the various areas of interface, between the prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm. CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate coverage of the tumor, while minimizing the volume of surrounding dose limiting normal tissues irradiated. This approach should in theory improve the tumor control and complication probabilities compared to using conventional treatment techniques and to using a 6-field conformal technique with uniform margins.

Comparison of treatment plans involving intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with conventional treatment plans for a case of locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: The study case was planned using two types of IMRT techniques, as well as a three-dimensional conformal radiotherapy technique (3D-CRT), and a traditional treatment method using bilateral opposing fields. These four plans were compared with respect to dose conformality, dose-volume histogram (DVH), dose to the sensitive normal tissue structures, and ease of treatment delivery. RESULTS: The planned dose distributions were more conformal to the tumor target volume in the IMRT plans than those in the conventional plans. With similar dose coverage of the clinical target volume (CTV), defined as delivery of minimum of 60 Gy to >/= 95% of CTV, the IMRT plans achieved better sensitive normal tissue structure sparing, while concomitantly delivering a minimum dose of 68 Gy to >/= 95% of the gross tumor volume (GTV) at a higher dose per fraction. CONCLUSIONS: Compared to conventional techniques, IMRT techniques provide improved tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced nasopharyngeal carcinoma. With improvement of the delivery efficiency, IMRT should provide the optimal treatment for all nasopharyngeal carcinoma. Further studies are needed to establish the true clinical advantage of this new modality.

Dose optimization for the treatment of anaplastic thyroid carcinoma: a comparison of treatment planning techniques.

PURPOSE: To evaluate and compare dose optimization for the treatment of anaplastic thyroid carcinoma using a 3D conformal plan, and two 3D intensity-modulated inverse plans. METHODS AND MATERIALS: After patient immobilization using an alpha cradle and head-mask system, a postoperative CT scan was obtained to delineate the gross tumor volume (GTV), the clinical tumor volume (CTV), and adjacent critical structures. Treatment plans were generated using UM-Plan (University of Michigan), PeacockPlan and Corvus (NOMOS Corporation, Sewickley, PA). Isodoses were displayed in the sagittal, coronal, and multiple axial planes, and dose-volume histograms (DVH) were generated for the GTV, CTV, and critical normal tissues. Treatment times were estimated to compare the practicality of delivering each plan in a busy radiotherapy department. RESULTS: All three treatment planning systems were able to deliver a minimum dose of 60 Gy to the GTV while keeping the maximum spinal cord dose at or below 45 Gy. However, there were differences in the doses delivered to 50% and 5% of the cord, the minimum CTV dose, and the overall treatment time. The PeacockPlan best spared the uninvolved tissues of the posterior neck, and provided the lowest dose to the cord without compromising the CTV. CONCLUSIONS: Inverse treatment planning provides superior dose optimization for the treatment of anaplastic thyroid carcinoma. The radiobiologic impact of intensity modulation for this tumor should be further tested clinically.

Endocrine function following high dose proton therapy for tumors of the upper clivus.

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

Neurovisual outcome following proton radiation therapy.

From February 1981 to January 1984, 20 patients with a tumor of the upper clivus received proton irradiation at the Harvard Cyclotron Laboratory. For 15 patients with known neurovisual status (including visual acuity, color vision, visual field, and fundus examinations) we obtained a cumulative dose-volume histogram (DVH) of the optic nerves (ON) and the optic chiasm. The prescribed tumor doses ranged from 66.6 to 74.4 Cobalt Gray Equivalent (CGE) with a daily fraction size of 1.8 to 2.1 CGE. CGE is used because modulated protons have an RBE of 1.1 compared to 60Co. The follow-up ranged from 30 to 68 months (median 52). Two patients developed, 10 and 36 months post irradiation, a progressive visual deterioration affecting both eyes. This was attributed to an ON and a chiasm injury in one patient and to bilateral ON injury in the other patient. In the first patient, the dose-volume analysis indicated that approximately half of the ON and of the chiasm had received 65 CGE and 55 CGE, respectively. In the second patient, it indicated that a quarter of the left ON (LON) had received 55 CGE whereas the dose to the right ON (RON) was significantly less. This patient had diabetes mellitus which may be a predisposing factor. From this study, a complication rate of 20% (1/5) is observed when a substantial portion of the ON is taken to 65 CGE, while it doesn't exceed 12.5% (2/16) and 7.5% (1/13) at 55 CGE for the ON and for the chiasm, respectively. This suggests a tolerance dose implying a 10% rate of major complications close to 55 CGE. When a tumor requires a high radiation-dose, the exclusion of these structures at 55 to 60 Gy is recommended.

Conservative treatment of uveal melanoma: local recurrence after proton beam therapy.

Twenty-three of 1006 (2.3%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986 received additional treatment for documented (15 patients) or suspected (eight patients) tumor growth in the irradiated eye. Growth within the initially irradiated volume was documented at Massachusetts Eye and Ear Infirmary in 12 patients. Documented growth occurred in nine of 665 (1.4%) patients with small and intermediate size tumors, at times after treatment ranging from 6 to 48 months (median 16 months), and in three of 341 (.9%) patients with large tumors at 7, 11, and 12 months after treatment. Melanoma growing totally outside the treated volume was also documented in three additional patients at 7, 9, and 45 months; two of these were thought to be "ring melanomas". Eight patients had the treated eye removed elsewhere for suspected tumor growth. The additional treatment in these 23 patients was conservative in nine patients (repeat proton irradiation in five and laser photocoagulation in four). Thirteen underwent immediate enucleation and one had orbital exenteration. Ultimately, 17 of the 23 eyes (74%) were removed. Estimated probability of local control of the melanoma within the irradiated eye at 60 months was 96.3 +/- 1.5%. Dose distributions to the 12 patients with documented local failure within the irradiated volume were analyzed. Ten tumors recurred marginally in an area receiving less than the prescribed dose of 70 CGE (CGE = Cobalt Gray Equivalents = proton Gy X RBE 1.1), whereas only two recurred in the volume receiving full dose. Based on these data, it appears that a dose of 70 CGE in five fractions is associated with very high rates of local control in human uveal melanoma. It is reasonable to consider initiating studies using a lower total dose or a more protracted course, to determine if some of the observed complications are dose-related.

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma.

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

Relative biological effectiveness of modulated proton beams in various murine tissues.

The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.