Long-term outcomes of patients with conjunctival extranodal marginal zone lymphoma.

Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%-79.8%) and 89.4% (95% CI 77.4%-95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%-35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1-2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08-7.95; p = .035, OS: HR = 9.07, 95% CI 1.17-70.26; p = .035) and MALT-IPI 1-2 (PFS: HR = 2.67, 95% CI 1.12-6.31; p = .027, OS: HR = 6.64, 95% CI 1.45-30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04-0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12-0.96 p = .041 and SHR = 0.11, 95% CI 0.03-0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.

NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients.

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1-3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

Uveal melanoma gene expression status post radiotherapy.

PURPOSE: Gene expression profiling has been shown to yield two distinct molecular genetic signatures for uveal melanoma. These class designations tend to predict tumor aggressiveness and the likelihood of metastasis. Tumors with a class 1 genetic signature are generally much less aggressive than tumors with a class 2 genetic signature. Gene expression analysis for previously treated uveal melanoma has not yet been reported. The authors report three cases where genetic analysis was successfully obtained from uveal melanoma that was previously treated years earlier with radiotherapy. CASE REPORT: The patients in all three cases received globe-conserving radiotherapy for treatment of choroidal melanoma before gene expression profiling was readily available. The patients in cases 1 and 2 received 125I plaque brachytherapy while the patient in case 3 received proton irradiation therapy. When secondary surgery was necessary to stabilize these eyes from the effects of radiation retinopathy, fine-needle aspiration biopsy was also performed for gene expression profiling. Genomic analysis revealed a class 1 molecular signature for the patient in case 1 and a class 2 molecular signature for the patients in cases 2 and 3. CONCLUSIONS: Gene expression profiling for uveal melanoma may be obtained from patients who were previously treated with radiotherapy; however, the implication of these results will benefit from ongoing clinical evaluation.

Predictors of Local Recurrence and Progression-Free Survival in Iodine-125 Brachytherapy-Treated Uveal Melanomas: A Modern Institutional Study.

Introduction: Iodine-125 brachytherapy is an effective eye-sparing treatment for uveal melanoma. Previous work has shown that uveal melanomas cluster into distinct molecular classes based on gene expression profiles - discriminating low-grade from high-grade tumors. Our objective was to identify clinical and molecular predictors of local recurrence (LR) and progression-free survival (PFS). Methods: We constructed a retrospective database of uveal melanoma patients from the University of Miami's electronic medical records that were treated between January 8, 2012, and January 5, 2019, with either COMS-style or Eye Physics plaque. Data on tumor characteristics, pretreatment retinal complications, post-plaque treatments, LR, and PFS were collected. Univariate and multivariate Cox models for cumulative incidence of LR and PFS were conducted using SAS version 9.4. Results: We identified 262 patients, with a median follow-up time of 33.5 months. Nineteen patients (7.3%) had LR, and 56 patients (21.4%) were classified as PFS. We found that ocular melanocytosis (hazard ratio = 5.55, p < 0.001) had the greatest impact on PFS. Genetic expression profile did not predict LR outcomes (hazard ratio = 0.51, p = 0.297). Conclusion: These findings help physicians identify predictors for short-term brachytherapy outcomes, allowing better shared decision making with patients preoperatively when deciding between brachytherapy versus enucleation. Patients stratified to higher risk groups based on preoperative characteristics such as ocular melanocytosis should be monitored more closely. Future studies must validate these findings using a prospective cohort study.

Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

BACKGROUND: A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. METHODS: We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. RESULTS: With a minimum of 2 years of follow-up (> or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group. CONCLUSIONS: Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].).

Dosimetric comparison of circular Eye Physics and Collaborative Ocular Melanoma Study plaques to treat uveal melanoma.

PURPOSE: We sought to formally compare Collaborative Ocular Melanoma Study (COMS) and similar-shaped (circular) eye physics (EP) plaques dosimetrically by examining both tumor coverage and critical structure doses. METHODS AND MATERIALS: The plans of patients with uveal melanoma treated consecutively with eye plaque brachytherapy at a single institution from January 2016 to December 2017 were reviewed. Both a COMS plan and an EP plan using plaques of the same shape were generated for each patient using the Isoaid Plaque Simulator software such that >90% of the tumor + 2 mm margin received 85 Gy over 72 hours from iodine-125 sources. Dose statistics were recorded and analyzed using standard statistical methods. RESULTS: Plans from a total of 62 patients were analyzed. The mean tumor volume was 0.46 cm3 (range: 0.02-2.02), and tumors were located on average 5.89 mm (range: 0-15.0) from the macula and 6.25 mm (range: 0-16.0) from the optic disc. All plans met the treatment planning criteria for tumor coverage and were optimized to reduce dose to the adjacent organs at risk. There were no significant differences in the mean doses to the fovea (mean difference [MD] = -0.87 Gy; 95% confidence interval [CI]: -4.90 to 3.16; p = 0.80), macula (MD = -1.02 Gy; 95% CI: -4.15 to 2.11; p = 0.65), or optic disc (MD = 1.07 Gy; 95% CI: -0.77 to 2.91; p = 0.34) between the COMS and circular EP plaques. CONCLUSIONS: Overall, neither the COMS plaques nor the circular EP plaques provided consistently superior dosimetry for the treatment of uveal melanoma. The choice of plaque may be based on other considerations such as cost and surgeon preference.

Are increased tumor aneuploidy and heightened cell proliferation along with heterogeneity associated with patient outcome for carcinomas of the uterine cervix? A combined analysis of subjects treated in RTOG 9001 and a single-institution trial.

PURPOSE: To look for possible associations between measurements of DNA index (DI), S-phase fraction (SPF), and tumor heterogeneity (TH) using flow cytometry and overall survival for patients with invasive cervical carcinoma treated with definitive irradiation. METHODS AND MATERIALS: A total of 57 patients with International Federation of Obstetrics and Gynecology Stages IB(2) through IVB cervical carcinomas treated with definitive radiotherapy with or without concurrent chemotherapy were enrolled into this registry study that involved flow cytometric analysis of fresh tissue from each cervical cancer obtained by pretreatment biopsy. These specimens were evaluated for DNA aneuploidy (DI 1.5), SPF (15%), and TH (uniploid vs. multiploid). RESULTS: In these analyses 27 of the patients were treated in Radiation Therapy Oncology Group protocol 9001, and an additional 30 were offered chemoradiation at a single institution. Forty-one patients had DI 1.5. Twenty-nine patients had SPF 15%, and 2 had no determinable SPF. Forty-three patients had uniploid and 14 multiploid tumors. The 4-year estimated overall survival rate for the entire study cohort was 62% (95% confidence interval 48%-74%). With a median follow-up of 3.7 years, there were no observable associations by univariate analysis for DI, SPF, or TH concerning patient survival. CONCLUSIONS: There were no statistically significant associations among DI, SPF, or TH and patient outcome. Additional studies are indicated to identify tumor biomarkers that could predict patients at risk for disseminated disease.

Association of Radiomics and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme.

PURPOSE: To build a framework for investigation of the associations between imaging, clinical target volumes (CTVs), and metabolic tumor volumes (MTVs) features for better understanding of the underlying information in the CTVs and dependencies between these volumes. High-throughput extraction of imaging and metabolomic quantitative features from magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging of glioblastoma multiforme (GBM) results in tens of variables per patient. In radiation therapy of GBM the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl aspartate (NAA) and choline (Cho). The corresponding clinical target volumes (CTVs) for radiation therapy are based on contrast-enhanced T1-weighted (CE-T1w) and T2-weighted (T2w)/fluid-attenuated inversion recovery MRI. METHODS AND MATERIALS: Necrotic portions, enhancing lesion, and edema were manually contoured on CE-T1w/T2w images for 17 GBM patients. Clinical target volumes and MTVs for NAA (MTVNAA) and Cho (MTVCho) were constructed. Imaging and metabolic features related to size, shape, and signal intensities of the volumes were extracted. Tumors were also scored categorically for 10 semantic imaging traits by a neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and CTVs/MTVs features were visualized as heatmaps. Associations between MTVNAA and MTVCho and imaging features were studied using Spearman correlation. RESULTS: Forty-eight imaging features were extracted per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. Twenty features were extracted from CTVs and MTVs. A series of semantic imaging traits were replaced with automatically extracted continuous variables. There were multiple (22) significant correlations of imaging measures with CTVs/MTVNAA, whereas there were only 6 with CTVs/MTVCho. CONCLUSIONS: A framework for investigation of codependencies between MRI and magnetic resonance spectroscopic imaging radiomic features and CTVs/MTVs has been established. The MTV for NAA was found to be closely associated with MRI volumes, whereas very few imaging features were related to MTVCho, indicating that Cho provides additional information to imaging.

Outcomes of iodine 125 plaque radiotherapy after initial observation of suspected small choroidal melanomas: a pilot study.

PURPOSE: To determine the visual and survival outcomes for patients undergoing plaque radiotherapy of suspected small choroidal melanomas after observation for growth in a pilot study. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-five patients with suspected small choroidal melanomas who were seen at the Bascom Palmer Eye Institute between 1974 and 2001 and had iodine 125 (I125) plaque radiotherapy between 1991 and 2002. METHODS: Patients with suspected small choroidal melanomas were monitored by clinical examination, photography, and echography. When the melanoma grew or developed orange pigment, patients were treated with I125 plaque radiotherapy. Outcomes included visual acuity, ocular complications, tumor dimensions, metastasis, and death. MAIN OUTCOME MEASURE: Melanoma-specific mortality. RESULTS: In our pilot study, 1 patient died from metastatic melanoma. One patient developed metastatic disease and is still alive. One patient developed marginal tumor recurrence after treatment and after enucleation was performed. Globe conservation was achieved in 97.8% of patients. In patients with tumor margins >2 mm from the optic nerve, vision was preserved with less than a doubling of the visual angle (within approximately 2 Snellen lines of preoperative acuity) in 90.6% (29/32) of patients at 1 year postoperatively, 65.6% (21/32) at 2 years, and 52.2% (12/23) in the long term (4-11 years). CONCLUSIONS: Five-year melanoma-specific mortality after I125 plaque radiotherapy of suspected small choroidal melanomas was 3.9% (95% confidence interval, 0%-11.2%). This information can be used to counsel patients with small suspected choroidal melanomas and to compare with other treatment modalities.

Pars plana lensectomy and intraocular lens implantation in pediatric radiation-induced cataracts in retinoblastoma.

OBJECTIVE: To investigate visual outcomes, surgical complications, and tumor recurrence among children with retinoblastoma (RB) undergoing pars plana lensectomy, vitrectomy, and simultaneous intraocular lens insertion for radiation-related cataract secondary to external beam radiotherapy (EBRT). DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: The medical records for all patients treated with pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens implantation for radiation-induced cataract after EBRT for RB at a single institution between January 1, 1990, and December 31, 2000, were reviewed. PARTICIPANTS: The study included 16 eyes of 12 children with Reese-Ellsworth stage V RB. MAIN OUTCOME MEASURES: Visual acuity, surgical and postoperative complications, postoperative refraction, and tumor recurrence. RESULTS: The median age at diagnosis of RB was 6 months (range, 1-49 months). All patients received EBRT as primary treatment and experienced radiation-induced cataracts. The median interval from RB diagnosis to cataract surgery was 42 months (range, 28-95 months). Preoperative mean visual acuity was 20/400, with 12 of 16 eyes (75%) having macular tumor involvement. All patients underwent pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens insertion. Vitreous samples were evaluated by cytopathologic examination, and no viable tumor cells were identified in any of the vitreous specimens. Postoperative complications included transient cystoid macular edema in 5 eyes (31%) and iridocyclitis in 3 eyes (19%). The mean follow-up after cataract surgery was 66 months (range, 30-94 months). Final visual acuity was 20/40 or better in 11 of 16 eyes (69%). No late intraocular recurrence, orbital tumors, or metastatic disease was noted in this study. CONCLUSIONS: Pars plana lensectomy, vitrectomy, and simultaneous intraocular lens implantation is an effective means of managing EBRT-induced cataracts in eyes with previously treated RB. There was no evidence of active tumor in eyes undergoing surgery at least 28 months after the diagnosis and commencement of therapy for RB, and no late intraocular, orbital, or metastatic tumors were detected. Visual acuity was limited by the presence of primary macular tumor pathologic features in a subset of patients, but final vision better than 20/400 may be achieved in these eyes.

Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV.

PURPOSE: This is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma. METHODS AND MATERIALS: A total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS: The average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up. CONCLUSION: Tolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.

Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II.

PURPOSE: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. MATERIALS AND METHODS: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. RESULTS: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. CONCLUSIONS: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of >/= Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.

Interim report of toxicity from 3D conformal radiation therapy (3D-CRT) for prostate cancer on 3DOG/RTOG 9406, level III (79.2 Gy).

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally tolerated radiation dose in men treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. This is a preliminary report of toxicity at Level III (79.2 Gy) on 3D Oncology Group/Radiation Therapy Oncology Group (RTOG) 9406. METHODS AND MATERIALS: Between November 26, 1996 and October 1, 1998, 173 patients with clinically organ-confined prostate cancer (T1 and T2) were accrued to a Level III dose of 79.2 Gy. One hundred sixty-nine patients were available for analysis of toxicity. Patients were registered to two groups according to the risk of seminal vesicle invasion (SVI) on the basis of presenting PSA and Gleason score. Group 1 patients had a calculated risk of SVI <15%, and Group 2 patients had a risk of SVI > or = 15%. For Group 1 patients, the planning target volume (PTV) margins were 5-10 mm around the prostate only. For Group 2 patients, the same margins were applied to the prostate and seminal vesicles (PTV(1)) for the initial 55.8 Gy; then treatment volume was reduced to the prostate only (PTV(2)). To reduce the rectal dose on dose Level III, the minimum PTV dose was limited to 73.8 Gy, whereas the minimum gross target volume dose was 79.2 Gy, both in 44 fractions. The incidence of > or = 3 Grade late effects was compared to that in a similar group of patients treated on RTOG 7506 and 7706 studies. RESULTS: Acute tolerance to 79.2 Gy was excellent with no patients experiencing > or = Grade 3 acute toxicity. The acute toxicity rate was comparable to that reported for previous lower dose levels. With the median follow-up of 3.3 years (range: 0.4-4.4 years), a total of 4 patients (2.4%) experienced Grade 3 late toxicity, three cases of which were related to the bladder, and one related to the rectum. There were no Grade 4 or 5 late complications noted during the period of observation. These results are also comparable to those reported at dose Levels I and II. The expected incidence of > or = 3 Grade 3 late toxicity was calculated using historical data from two previous RTOG prostate cancer trials, 7506 and 7706. The calculated risk accounted for the difference in follow-up duration between patients in this study and the historical experience. The observed rate of > or = Grade 3 late effects for Group 1 (two cases) is significantly lower (p = 0.0002) than the 17.6 cases that would have been expected from the historical control. The observed rate for Group 2 (two cases) was also significantly lower (p = 0.0037) than the 12.1 cases expected. CONCLUSION: Based on excellent tolerance of 3D-CRT for stages T1 and T2 prostate cancer, further biological dose escalation has been pursued to Levels IV and V, 74 Gy and 78 Gy, respectively, at 2 Gy per day, in an attempt to reduce the total treatment duration. This trial has closed. A Phase III comparative RTOG trial is being developed to determine whether high-dose 3D-CRT improves efficacy.

Hyperfractionated external beam radiation therapy in the treatment of murine transgenic retinoblastoma.

OBJECTIVE: To determine the in vivo efficacy of hyperfractionated external beam radiation therapy (EBRT) in comparison with standard daily EBRT in a murine model of heritable retinoblastoma. METHODS: Two hundred twenty eyes from 6-week-old simian virus-40 large T-antigen--positive mice were treated with a total dose of EBRT ranging from 10-76 Gy (1000 to 7600 rad). One hundred ten eyes underwent EBRT administered in 2.0-Gy (200-rad) fractions once per day. Forty-two eyes received hyperfractionated EBRT administered in 1.2-Gy (120-rad) fractions twice per day, while 48 eyes received EBRT twice daily in fractions of 5.0 Gy (500 rad). Twenty eyes served as untreated controls. All eyes were obtained for histopathologic examination and graded positive if any tumor was present. RESULTS: A dose-dependent inhibition of ocular tumor was observed for EBRT in these transgenic retinoblastoma mice. The tumor control dose for 50% of eyes (TCD(50)) treated with 2.0 Gy fractions of EBRT was 45 Gy (4500 rad) when treatments were administered once daily. A significant increase in tumor control was observed when treatments were administered twice per day at fractions of 1.2 Gy, resulting in a TCD(50) of 33 Gy (3300 rad) (P =.003). A further increase in tumor control was observed when twice-daily EBRT was administered in 5.0 Gy fractions resulting in a TCD(50) of 28 Gy (2800 rad). CONCLUSIONS: Hyperfractionated EBRT safely and effectively controls intraocular retinoblastoma in this transgenic animal model. Use of hyperfractionation allows for a reduction in total radiation delivered dose, while shortening the total treatment time. CLINICAL RELEVANCE: This treatment approach may be applicable in the management of pediatric retinoblastoma by maintaining excellent tumor control, while reducing treatment-associated complications.

External beam radiation "salvage" therapy in transgenic murine retinoblastoma.

OBJECTIVE: To determine the efficacy of low-dose "salvage" external beam radiation therapy (EBRT) following failed subconjunctival carboplatin chemotherapy in a murine model of heritable retinoblastoma. METHODS: Eighty-four eyes from 8-week-old, simian virus 40, T-antigen-positive mice were treated with 6 serial subconjunctival carboplatin injections (100 microg/25 microL). At 12 weeks of age, 64 eyes received EBRT for a total dose of 480 (4.8 Gy), 1200 (12.0 Gy), 1560 (15.6 Gy), or 3000 (30.0 Gy) rad. Twenty eyes received no additional therapy following subconjunctival carboplatin injections. Ten eyes received a total dose EBRT of only 3000 rad. Eight eyes received subconjuctival injections of only an isotonic sodium chloride solution. Ten eyes served as untreated controls. MAIN OUTCOME MEASURES: Eyes were enucleated at 20 weeks to assess the presence of tumor on histopathological examination. RESULTS: Salvage therapy using low-dose EBRT was able to reestablish tumor control in a dose-dependent manner. Increasing the EBRT dose to 3000 rad resulted in 100% tumor control. The dose-dependent curves were significantly different between the treatment groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (P<.001). CONCLUSION: Low-dose hyperfractionated salvage EBRT following failed primary subconjunctival carboplatin chemotherapy is efficacious in the treatment of retinoblastoma in this animal model. Clinical Relevance Salvage EBRT using a reduced total radiation dose could be associated with a radiation-related treatment enhancement in pediatric retinoblastoma.

Eyelid and scleral necrosis following bare iridium-192 seed for retinoblastoma.

A 2 1/2-year-old girl with a history of bilateral retinoblastoma underwent primary enucleation of the right eye and was referred for further management of persistent tumor in the fellow eye. Previous treatment of the left eye included external beam radiotherapy, systemic chemotherapy, laser photocoagulation, cryotherapy, and direct scleral application of a bare iridium-192 radioactive seed. Examination revealed focal full-thickness necrosis of the left upper and lower eyelid and a large inferonasal viable retinoblastoma tumor with overlying retinal detachment. Systemic chemotherapy and direct laser photocoagulation were administered. Four months after presentation, the patient developed focal scleral necrosis with 360 degrees hemorrhagic choroidal detachment. Enucleation was performed and histopathologic examination demonstrated full-thickness scleral necrosis with adjacent viable retinoblastoma tumor cells. Follow-up examinations showed no evidence of recurrent or metastatic tumor. This case is the first report of scleral necrosis following combined modality treatment of retinoblastoma.

Spectral-domain optical coherence tomography evaluation of choroidal melanoma and nevus fine-needle aspiration biopsy incision sites.

The authors present three cases in which spectral-domain optical coherence tomography was used to identify fine-needle aspiration biopsy incision sites. These biopsies were performed to obtain tissue for gene expression profiling of choroidal tumors. A transvitreal route into the apex of the tumors was utilized for the biopsies while the patients underwent pars plana vitrectomy, membrane peel, laser ablation, phacoemulsification with posterior chamber intraocular lens implantation, and intravitreal triamcinolone acetonide. To the best of the authors' knowledge, this is the first report documenting fine-needle aspiration biopsy incision wound architecture of the posterior segment with optical coherence tomography.

Novel Use of Endoscopic Clips as Fiducials for Radiotherapy in Small Bowel Lymphoma.

A 31-year-old woman was diagnosed with duodenal grade 1 follicular lymphoma. The patient underwent radiotherapy and on surveillance enteroscopy, the lymphoma was persistently identified in the duodenum and jejunum. Endoscopic clips were used as fiducials to better localize the tumor during radiotherapy. Endoscopic clips are increasingly used as tumor localization tools because of their favorable risk-benefit ratio. In our case, endoscopic clipping was necessary to properly localize the tumor after prior treatment failure, and the patient now has no evidence of disease. Larger studies are needed to demonstrate the efficacy of clips in tumor localization and improved disease-related morbidity.