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%.

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.

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.

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience.

PURPOSE: To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION: 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.

The value of nonuniform margins for six-field conformal irradiation of localized prostate cancer.

PURPOSE: Evaluate the hypothesis that by combining nonuniform margins with a technique for limiting the possible extent of posterior motion of the prostate during the delivery of six-field conformal radiotherapy (SFCRT) of the prostate, it is possible to adequately treat the clinical target volume (CTV) and minimize dose to normal structures. METHODS AND MATERIALS: Serial computed tomography (CT) scans of prostate patients were taken at 0.5 cm intervals for treatment planning purposes. The initial treatment planning scans were performed with the rectum empty and the bladder full. Subsequent scans were taken at the end of the first week of treatment with the bladder full, but with no attempt to empty the rectum, to mimic the typical treatment situation. The gross tumor volume (GTV), consisting of the prostate and seminal vesicles, as well as the CTV, were defined on the CT images with the aid of a urethrogram to define the inferior border (apex) of the prostate. Variable blocking margins were designed around the CTV using the University of Michigan three dimensional (3D) treatment planning system (UM-PLAN). Isodose distributions displayed on axial, sagittal, coronal, and oblique slices were used to evaluate the adequacy of the various margins applied. Nonuniform margins varying from 0.75 cm posteriorly to 2.0 cm anteriorly and inferiorly were compared to uniform margins of 1.0, 1.5, and 2.0 cm for each patient. Dose volume histograms (DVH) were used to compare doses to the GTV, CTV, rectum, and bladder. RESULTS: In a series of 10 patients scanned with the above protocol, treatment plans with nonuniform margins were compared with uniform margins of 1.0, 1.5, and 2.0 cm. Dose-volume histograms showed that nonuniform and 1.0 cm uniform margins deliver the lowest doses to the rectum and bladder, but the use of 1.0 cm uniform margins resulted in inadequate coverage of the CTV in 40% of the cases. The 1.5 and 2.0 cm uniform margins adequately covered the CTV but resulted in significantly higher doses to the bladder and rectum. CONCLUSIONS: The use of nonuniform margins, when combined with CT scans performed with the rectum empty and bladder full, can improve tumor control probability while minimizing the risk of morbidity to adjacent critical structures.

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.

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.