Impact of Neuroradiology-Based Peer Review on Head and Neck Radiotherapy Target Delineation.

BACKGROUND AND PURPOSE: While standard guidelines assist in target delineation for head and neck radiation therapy planning, the complex anatomy, varying patterns of spread, unusual or advanced presentations, and high risk of treatment-related toxicities produce continuous interpretive challenges. In 2007, we instituted weekly treatment planning quality assurance rounds as a joint enterprise of head and neck radiation oncology and neuroradiology. Here we describe its impact on head and neck radiation therapy target delineation. MATERIALS AND METHODS: For 7 months, treatment planning quality assurance included 80 cases of definitive (48%) or postoperative (52%) head and neck radiation therapy. The planning CT and associated target volumes were reviewed in comparison with diagnostic imaging studies. Alterations were catalogued. RESULTS: Of the 80 cases, 44 (55%) were altered, and of these, 61% had clinically significant changes resulting in exclusion or inclusion of a distinct area or structure. Reasons for alteration included the following: gross or extant tumor, 26/44 (59%); elective or postoperative coverage, 25/44 (57%); lymph nodes, 13/44 (30%); bone, 7/44 (16%); skull base, 7/44 (16%); normal organs, 5/44 (11%); perineural, 3/44 (7%); distant metastasis, 2/44 (5%); and eye, 1/44 (2%). Gross tumor changes ranged from 0.5% to 133.64%, with a median change in volume of 5.95 mm3 (7.86%). Volumes were more likely to be increased (73%) than decreased (27%). CONCLUSIONS: A collaborative approach to head and neck treatment planning quality assurance has an impact. Cases likely to have challenging patterns of infiltrative, intracranial, nodal, orbital, or perineural spread warrant intensive imaging-based review in collaboration with a diagnostic neuroradiologist.

Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.

PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival. METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC. RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT. CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.

Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival.

BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) has been dismal. The objective of this study was to identify prognostic factors in patients who had prolonged survival. METHODS: Patients with ATC were identified from a computer database at a tertiary referral center. Univariate and multivariate analyses for survival differences were performed using the Kaplan-Meier log-rank statistic and the Cox proportional hazards model, respectively. RESULTS: Of the 33 evaluable patients, median survival was 3.8 months. Median age was 69 years. Prior goiter was present in 6 patients (18%), and 6 (18%) had prior thyroid carcinoma. Median tumor size was 6 cm, and 12 (36%) had adjacent well-differentiated carcinoma. Of the 26 patients who underwent neck exploration, 8 patients were potentially cured and received postoperative chemotherapy and irradiation; 4 (50%) were surgically macroscopically free of disease, and 4 (50%) patients had minimal residual disease after total thyroidectomy and resection of tumor adherent to adjacent structures. Four of these 8 patients survived longer than 2 years; their 5-year survival estimate was 50%. Eighteen patients underwent palliative resection of neck disease, leaving macroscopic residual disease or distant metastases; postoperative adjuvant chemotherapy and irradiation were administered in 16 of these 18 patients. Seven patients were treated with only chemotherapy and irradiation. In patients treated with potentially curative resection, median survival was 43 months compared with 3 months with palliative resection (P =0.002); the median survival of 3.3 months with only chemotherapy and irradiation was no different than palliative resection (P =0.63). No association was found between survival and age, prior goiter, prior thyroid carcinoma, adjacent differentiated carcinoma, or tumor size. CONCLUSIONS: Although the prognosis of most patients with ATC continues to be poor, complete resection of ATC combined with postoperative adjuvant chemotherapy and irradiation resulted in long-term survival, even with persistent minimal disease that remained on vital structures. An aggressive attempt at maximal tumor debulking followed by adjuvant therapy was found to be warranted in patients with localized ATC.

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.

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.

15 years experience with helium ion radiotherapy for uveal melanoma.

PURPOSE: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. METHODS AND MATERIALS: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. RESULTS: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of 20/200 or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. CONCLUSIONS: Local control and retention of the eye are excellent. Complications of therapy reduce vision and eye preservation. Twenty-four percent of patients manifested distant metastases 6 to 146 months posttreatment, mean of 43 months, median of 36 months. Late-appearing distant metastases do not appear to be caused by persistent tumor in the eye. The risk of metastases is high for patients with tumors greater than 7 mm in initial ultrasound height (37%), anterior tumors involving the ciliary body (47%), and in those with local failure (53%). Patients with tumors not involving the ciliary body and initial dimensions less than 10 mm had only an 8% chance of death from melanoma. A search for effective adjuvant therapy is needed for patients at high risk of metastases (large tumors, ciliary body involved, local regrowth in eye).

Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma.

OBJECTIVE: The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. DESIGN: The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. PARTICIPANTS: Seven hundred sixty-six posterior uveal melanoma patients were studied. INTERVENTION: Either iodine-125 plaque or helium ion radiation therapy was performed. MAIN OUTCOME MEASURES: Local tumor recurrence and systemic metastasis were measured. RESULTS: Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. CONCLUSIONS: Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.

Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma.

PURPOSE: To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was < 1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0-2.24 Gy in 62, and > or = 2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3-436 months). RESULTS: Five-year local control was 85% for T1 and 70% for T2 glottic carcinomas (p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor (p = 0.02), and anterior commissure (AC) involvement was of borderline significance (p = 0.056). Five-year local control was 77% for patients treated between 1956-1970, 89% for between 1971-1980, and 91% for between 1981-1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time (p = 0.003), fraction size (p = 0.003), total dose (p = 0.01), impaired vocal cord mobility (p = 0.02), and subglottic extension (p = 0.04). Five-year local control was 100% for T2 lesions treated with overall time < or = 43 days vs. 84% for overall time > 43 days; 100% for fraction size > or = 2.25 Gy vs. 44% for fraction size < 1.8 Gy; 78% for total dose > 65 Gy vs. 60% for total dose < or = 65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. CONCLUSIONS: Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

125I plaque therapy for uveal melanoma. Analysis of the impact of time and dose factors on local control.

BACKGROUND: 125I episcleral plaque therapy has gained wide acceptance for the treatment of uveal melanoma because of its potential to preserve vision, salvage the globe, and provide good local control. A rigorous analysis of the optimum radiation dose, dose rate, and overall treatment time has not been reported with this technique. METHODS: One hundred fifty patients with uveal melanoma treated with 125I plaques between 1982 and 1990 and included in the uveal melanoma study (UMS) database of the Wills Eye Hospital were analyzed. Mean patient age was 60.7 years (range: 17.7-84.6 years). Initial mean tumor size was 9.7 x 8.5 x 3.7 mm with a range of 4.5 to 21.5 mm in basal dimension and 1.2 to 11.8 mm in height. Mean dose to the tumor apex was 94.77 gray (Gy) (29.5-141 Gy). Mean dose rate to the tumor apex was 92.9 cGy/hr (10-292 cGy/hr); the mean dose to the base was 359 Gy (181-692 Gy); the mean dose rate to the base was 348 cGy/hr (112-893 cGy/hr); and mean duration of treatment was 124.7 hours (range: 28-333 hours) RESULTS: With a median follow-up of 68 months, there have been 33 local failures. Mean time to local failure was 19 months (range: 6-78 months). Actuarial local control is 81% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger tumor dimension (P = 0.0046), close proximity to the optic disc (P = 0.0029), lower radiation dose to the tumor apex (P = 0.03), lower radiation dose rate to the tumor apex and base (P = 0.01 and 0.03), and longer overall treatment time (P = < 0.0001). CONCLUSIONS: This retrospective analysis reinforces the importance of dose rate, minimum tumor dose, overall treatment time, maximum tumor basal dimension, and proximity to the optic nerve in the treatment of uveal melanoma.

Long term visual outcome of radiated uveal melanomas in eyes eligible for randomisation to enucleation versus brachytherapy.

AIMS: To determine the long term visual outcome of patients who were eligible for randomisation to enucleation versus brachytherapy in a US collaborative ocular melanoma study (COMS) but were treated with either helium ion or 125I radioactive plaque therapy. METHOD: A retrospective analysis was performed of 426 ciliochoroidal melanomas that met COMS inclusion criteria for randomisation to enucleation versus radioactive plaque but were treated with either helium ions or 125I brachytherapy. RESULTS: At 3 years 36.0% of eyes had 6/12 or better visual acuity. The length of visual retention was most dependent on tumour thickness, tumour location with respect to the optic nerve, fovea, or ciliary body, and patient age. In addition to these factors, the retention of 6/12 visual acuity and the time to 6/120 visual acuity were dependent on the preoperative visual acuity. The risk of visual loss was greatest immediately after treatment and decreased with time. The 5 year actuarial metastatic rate was approximately 13%. Patients at the greatest risk of post-radiation visual loss had significantly greater risk of tumour related mortality. CONCLUSIONS: Some patients who would have been eligible for randomisation to either enucleation or radioactive plaque therapy can be irradiated with retention of excellent vision.

31P magnetic resonance spectroscopy after combined hyperthermia and radiation.

Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of changes that have been detected immediately after tumor treatment to differentiate successful from ineffective therapy. In this study we used in vivo 31P magnetic resonance spectroscopy (MRS) to assess intra-tumor treatment alterations. The metabolic consequences of effective and ineffective levels of solitary hyperthermia and combined hyperthermia-radiation were investigated. We have previously noted a characteristic 31P MRS pattern with successful hyperthermia in this intraocular melanoma model. The metabolic response after effective or ineffective combined radiation/hyperthermia therapy was indistinguishable from solitary radiation therapy and opposite to that with successful hyperthermia therapy. In contrast to solitary hyperthermia therapy, early changes in 31P spectral ratios following radiation or combined hyperthermia/radiation therapy of uveal melanoma were not predictive of treatment response. Twenty-four to 48 hours after effective or ineffective radiation or combined treatment the Pi/beta-NTP ratio decreased significantly (delta Pi/beta-NTP = -0.433 +/- 0.08 and -0.478 +/- .13 and .10 +/- 0.2, respectively). There was over a 2.0 thermal enhancement of radiation with heat. The increased tumor cell death after combined therapy was reflected by a two-fold larger decrease in beta-NTP signal-to-noise (S/N).

Irradiation of the cervix uteri: value of unenhanced and contrast-enhanced MR imaging.

PURPOSE: To analyze the value of magnetic resonance (MR) imaging after radiation therapy for cancer of the cervix. MATERIALS AND METHODS: Eighty-nine MR images were retrospectively studied in 69 patients aged 46.3 years +/- 11.5. MR findings of tumor recurrence and irradiation changes were correlated with time after radiation therapy; paracentral radiation dose (dose to point A); and in patients with pretreatment images, primary tumor size and stage. RESULTS: Overall accuracy of MR in diagnosis of tumor recurrence was 78% (positive predictive value, 65%; negative predictive value, 97%). In MR examinations less than 6 months after the beginning of radiation therapy, accuracy (69%) and specificity (46%) were significantly lower than in examinations more than 6 months later (88%, P = .0032; 81%, P = .0166, respectively). Comparison of pre- and posttreatment MR findings and knowledge of stage or initial tumor size did not affect MR results. CONCLUSION: Overall, diagnosis was best with unenhanced T2-weighted images, but in patients with adnexal or pelvic sidewall recurrence and in patients with treatment complications (eg, fistula formation), contrast enhancement did help.

Carcinoma of the cervix: predictive value of clinical and magnetic resonance (MR) imaging assessment of prognostic factors.

PURPOSE: This retrospective study assesses the predictive value of magnetic resonance imaging (MRI) to identify high risk cervical cancer patients. METHODS AND MATERIALS: The MRI evaluation of morphologic risk factors in patients with invasive cervical carcinoma treated with definitive radiation therapy were correlated with clinical factors and with complete tumor regression (CTR) at 6 months, tumor local control (TLC), and patient outcome at 12 months after irradiation. Sixty-six patients, median age 44.5 years, with bulky Stage I or greater disease were included in the study. RESULTS: In univariate analysis, clinical International Federation of Gynecology and Obstetrics (FIGO) stage had significant correlation with patient outcome, but it correlated poorly with complete tumor regression and tumor local control. In contrast, MRI stage showed significant correlation with complete tumor regression, tumor local control, and disease-free survival at 12 months. When each stage was analyzed separately, the greatest difference was demonstrated between clinical and MRI assignment of stage Ib disease. MRI Stage Ib disease significantly correlated with all three categories analyzed, while clinical Stage Ib did not. Superiority of MRI assessment of low stage disease was also evident in the detection of lymph node metastasis. Significant risk for nodal metastasis was related to tumor size greater than 4 cm, invasion of the parametria and urinary bladder, and stage of the disease. CONCLUSION: The multivariate analysis demonstrated that the most related variables in order of significance were the presence of juxta-regional and paraaortic lymph nodes, patient age, tumor size, and MRI tumor stage. This study demonstrates the value of MR imaging as an adjunct to clinical assessment of bulky invasive cervical cancer, rendering more complete assessment of morphologic risk factors important in patient prognosis.

Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial.

PURPOSE: Optimal radiation therapy for uveal melanoma is uncertain, and the relative efficacies of radioactive plaques and charged particles are unclear. METHODS: The authors prospectively studied helium-ion irradiation and iodine 125 (125I) brachytherapy in a randomized, dynamically balanced trial. Of the 184 patients who met the eligibility criteria, 86 were treated with helium ions and 98 with 125I brachytherapy. RESULTS: No patients with uveal melanoma had a history of systemic malignancy. Tumors were less than 15 mm in maximum diameter and less than 10 mm in thickness. A minimum tumor dose of 70 GyE was delivered to the tumor apex. There was a significantly higher local recurrence rate after 125I brachytherapy than after helium-ion irradiation. Enucleations occurred more frequently after brachytherapy (relative risk = 1.99; 95% confidence interval, 0.78-5.78). More anterior segment complications occurred after helium-ion irradiation. To date, there has been no measurable impact on survival. CONCLUSIONS: Most uveal melanomas can be managed with radiation with retention of the eye. There was better tumor control with helium-ion irradiation; however, there were more anterior segment complications.

High intensity 125-iodine (125I) plaque treatment of uveal melanoma.

PURPOSE: Episcleral 125I plaque therapy of uveal melanoma is an important treatment modality to control tumor, salvage the globe, and potentially preserve vision. We retrospectively analyzed our experience in 239 patients to assess treatment outcome with this technique. METHODS AND MATERIALS: Between 1983 and 1990, 239 uveal melanoma patients were treated with 125I plaques at the University of California, San Francisco. High intensity 125I seeds in the range of 3-20 mCi were used to give a minimum tumor dose of 70 Gy in 4 days. Initial mean tumor size was 10.9 mm x 9.2 mm x 5.5 mm with a range in tumor diameter from 4 to 18 mm and tumor height from 1.9 to 11.1 mm. Best corrected pre-treatment visual acuity was 20/200 or better in 92% of patients. RESULTS: Local tumor control was maintained in 91.7% of patients with a mean follow-up of 35.9 months; 19 patients had local tumor progression; mean time to progression was 27.3 mo (1.8 to 60.1 mo). Actuarial local control is 82% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger maximum tumor diameter (p = 0.0008), closer proximity to the fovea (p = 0.0001), lower radiation dose (p = 0.0437), and smaller ultrasound height (p = 0.0034). The actuarial incidence of distant metastases is 12% at 5 years with multivariate analysis showing significant correlation only with maximum tumor diameter (p = 0.0064). Visual outcome is 20/200 or better in 58% of patients. CONCLUSION: While the tumor control rates appear favorable, ocular morbidity is significant. A current randomized trial comparing 125I plaque with Helium ion therapy is in progress with specific comparison of tumor control, survival, and visual outcome.

Radiation therapy of acquired immunodeficiency syndrome-related Kaposi's sarcoma of the eyelids and conjunctiva.

We retrospectively studied 42 men with acquired immunodeficiency syndrome-related Kaposi's sarcoma of the conjunctiva or eyelids who were treated with radiation. Forty-nine sites were treated, 35 (71%) of which involved the eyelids, 12 (24%) the conjunctiva, and two (4%) both the eyelids and conjunctiva. Group 1 consisted of 31 sites treated with a single dose of 800 cGy and group 2 consisted of 18 sites treated with a multiple-fraction regimen and total doses between 1500 and 3600 cGy. The response and recurrence rates in the two groups were similar. One patient from group 2 died within 1 month of treatment and was not included in the analysis. The lesions improved in all cases. A complete response was obtained in 10 (32%) of the 31 lesions in group 1, compared with four (22%) of 18 lesions in group 2. A partial response was obtained in 21 (68%) of 31 lesions in group 1, compared with 13 (72%) of 18 lesions in group 2. Expected minor reactions in the treatment field, primarily loss of cilia, were comparable in the two groups. No serious complications were noted. Recurrence occurred in seven (22%) of the 31 sites in group 1 (six patients) and seven (39%) of the 18 sites in group 2 (six patients). The results suggest that a single treatment of 800 cGy is a safe and effective palliative therapy for ophthalmic acquired immunodeficiency syndrome-related Kaposi's sarcoma.

Acquired immunodeficiency syndrome-related Kaposi's sarcoma of the male genitalia: management with radiation therapy.

Kaposi's sarcoma of the genitalia is an infrequent complication of the acquired immunodeficiency syndrome but it often is difficult to manage. A total of 19 men (mean age 39 years) with penile and/or scrotal lesions underwent radiotherapy at dosages of 600 to 3,000 cGy. in fractions of 150 to 800 cGy. Of the patients 6 achieved a complete and 10 a partial response, while 2 had no response and 1 died too soon after treatment to be evaluated. Recurrences were noted in 8 patients, 7 of whom received additional radiation (1 patient had 2 recurrences and both responded). Of the retreatments 3 effected complete and 4 partial responses. Over-all, of 25 evaluable treatment courses 9 complete (36%) and 14 partial (56%) responses yielded a total response rate of 92%. There was 1 complication, a skin ulceration. Radiation therapy is well tolerated and will result in effective palliation in the majority of patients with Kaposi's sarcoma of the genitalia.

31P magnetic resonance spectroscopy (MRS) of experimental orbital myositis.

We described a model of orbital myositis that was induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) injection into the superior rectus muscle of New Zealand white rabbits. In this study, in vivo 31P magnetic resonance spectroscopy (MRS) was performed with a 4.7 Tesla Oxford (Oxford Instruments, Oxford, England) magnet to monitor the evolution of muscle inflammation in control animals and the response of this model to external beam radiation. 31P MRS showed a dramatic increase in high-energy phosphorus and phospholipid metabolites 48 hr after TPA injection. These spectra were similar to those from implanted allogenic fibroblasts. Within 18-48 hr after a single dose (400 cGy) or sequential doses (3 days at 400 cGy) of orbital irradiation, reduced extraocular muscle swelling and a significant decrease of all 31P metabolites occurred. A decrease (63 +/- 6%) in the signal-to-noise (S/N) ratio of the control inflamed muscle 31P MR spectra increased by 28 days after inflammation. Two days after single-dose radiation, 31P MR metabolites were significantly lower (58 +/- 5%, P less than 0.012) than control spectra. These postradiation spectra mirror the 28-day control spectra and are consistent with previous histologic data that show decreased fibroblastic activity. Change in 31P MRS was a sensitive indicator of treatment response latency.

Uveal melanoma: development of metastases after helium ion irradiation.

Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075).

Evaluation of acute radiation optic neuropathy by B-scan ultrasonography.

We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.