Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors.

OBJECTIVE: To evaluate the clinical factors predictive for tumor recurrence and treatment complications in a large series of children who underwent plaque radiotherapy for retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The participants included 141 children with retinoblastoma who were managed on the Oncology Service at Wills Eye Hospital with plaque radiotherapy between July 1976 and June 1999. MAIN OUTCOME MEASURES: Tumor recurrence and treatment complications. RESULTS: There were 208 tumors managed with plaque radiotherapy. The mean patient age at plaque treatment was 19 months. Prior treatment to the retinoblastoma of concern was delivered to 148 tumors (71%) and included various combinations of treatments such as intravenous chemoreduction, external beam radiotherapy, laser photocoagulation, thermotherapy, and cryotherapy. For 72 retinoblastomas (35%), more than one therapeutic method had failed to achieve tumor control before the use of plaque radiotherapy. Of the 208 retinoblastomas managed with plaque radiotherapy, Kaplan-Meier estimates of tumor control were 83% at 1 year and 79% at 5 years. Of the 60 tumors treated only with plaque radiotherapy (primary treatment), recurrence at 1 year was 12%. Of the 148 tumors treated after failure of other methods (secondary treatment), specific Kaplan-Meier estimates of tumor recurrence at 1 year was detected in 8% of tumors previously treated with chemoreduction, 25% of tumors previously treated with external beam radiotherapy, 34% tumors previously treated with both chemoreduction and external beam radiotherapy, and 8% of tumors previously treated with laser photocoagulation, thermotherapy, or cryotherapy (methods other than chemoreduction and external beam radiotherapy). Using multivariable analysis, the risks for tumor recurrence included the presence of tumor seeds in the vitreous, presence of subretinal tumor seeds, and increasing patient age. Using Kaplan-Meier estimates, radiation complications at 5 years of follow-up included nonproliferative retinopathy in 27%, proliferative retinopathy in 15%, maculopathy in 25%, papillopathy in 26%, cataract in 31%, glaucoma in 11%, and scleral necrosis in 0%. CONCLUSIONS: Plaque radiotherapy for retinoblastoma provides tumor control in 79% of cases at 5 years of follow-up. It is particularly useful for those tumors that fail treatment with chemoreduction, laser photocoagulation, thermotherapy, and cryotherapy. Tumors in young patients without vitreous or subretinal seeding show the best long-term control.

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

OBJECTIVE: To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. DESIGN: Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. PARTICIPANTS: Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. MAIN OUTCOME MEASURES: Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). RESULTS: Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. CONCLUSIONS: Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Radiotherapy for unilesional mycosis fungoides.

PURPOSE: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. METHODS AND MATERIALS: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. RESULTS: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. CONCLUSION: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Concomitant irradiation and dose-escalating carboplatin for locally advanced carcinoma of the uterine cervix: an updated report.

The combination of radiotherapy and carboplatin is associated with high response rates among women who have cervical cancer. To improve control rates for patients who have locally advanced carcinoma of the uterine cervix, oncologists have explored combinations of radiotherapy and chemotherapy. Carboplatin is an analogue of cisplatin, with similar efficacy against cervix cancer and a toxicity profile that is theoretically appealing for this group of patients because it is not nephrotoxic. Fifteen women with International Federation of Gynecology and Obstetrics (FIGO) stages IB2 through IIIB or recurrent carcinoma of the cervix were treated with megavoltage irradiation and weekly intravenous carboplatin (7 women, 60 mg/m2; 8 women, 90 mg/m2). Response was documented among all patients treated at 60 mg/m2 (three complete responses, four partial responses) and in 6 women treated with 90 mg/m2 (four complete responses, two partial responses). The two nonresponders in the series presented with recurrent glassy cell carcinoma of the cervix. All patients completed the planned course of therapy without the need for treatment interruption. At 60 mg/m2, one dose of carboplatin was withheld because of grade 2 thrombocytopenia. At 90 mg/m2, one case of grade 2 leukopenia was documented. The leukocyte counts remained within normal limits for all 3 patients who were irradiated through extended portals that encompassed the paraaortic nodes (2 women, 60 mg/m2; 1 woman, 90 mg/m2). To date, 2 of 7 patients treated at the lower dose level have died of disease (one local progression and distant failure at 11 months, one distant failure alone at 6 months). The remaining patients treated at 60 mg/m2 are alive at a median of 24 months (range, 21-37 months). Among those treated at the higher dose level, 1 patient is alive with local and distant failure at 14 months, and 1 woman succumbed to local and distant disease at 4 months. The remainder are alive at a median follow-up of 6 months (range, 2-10 months). The regimen was unsuccessful in salvaging women with recurrent glassy cell carcinoma. We conclude that the combination of radiotherapy and carboplatin can be safely delivered at both of the chemotherapy schedules studied. The regimen should not be offered to women who have recurrent glassy cell tumors. To prove the efficacy of this approach, phase III testing should be considered that compares the combination of agents to irradiation alone.

Radiation therapy for macular degeneration: technical considerations and preliminary results.

PURPOSE: This study was undertaken to assess the toxicity and possible benefits from the administration of low-dose external-beam irradiation for Age-Related Macular Degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neo-vasculature, resulting in reabsorption of fluid and blood thus reducing the risk for further leakage or bleeding, as well as subretinal fibrosis. Clinically, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet type of ARMD with the possibility for some visual improvement. METHODS AND MATERIALS: Allegheny University Hospitals, Hahnemann, Department of Radiation Oncology, treated 278 patients prospectively beginning in January 1995 with low-dose irradiation for wet-type macular degeneration. Two hundred forty-nine patients were treated with a total dose of 14.40 Gy in eight fractions of 1.80 Gy over 10-13 elapsed days, and 27 patients with 20 Gy at 2 Gy per fraction over 12-15 days. The first two patients were treated to a total dose of 10.00 Gy in five fractions of 2.00 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. A percentage (36.7%) of the patients had previously received laser treatments in the study eye, 21.9% once, 5% twice, 9.7% three or more. Subjective visual acuity and toxicity data was collected on all patients. RESULTS: At 2-3 weeks after treatment 195 patients (70%) retained their visual acuity without change, 68 patients (24.5%) stated they had improved vision, and 15 patients (4.8%) stated their vision continued to decrease. Two to 3 months after treatment, 183 patients (65.8%) had no change in their vision, 75 patients (27%) had an improvement in their vision, and 20 patients (7.2%) had a decrease in visual acuity. Transient acute reactions occurred in 14 of the 278 patients treated. CONCLUSION: Our observations in this group of 278 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age related wet type macular degeneration.

Intracavitary brachytherapy for carcinoma of the esophagus.

Local control of unresectable esophageal carcinomas remains a significant problem in spite of aggressive treatments. External beam radiation therapy, chemotherapy, and combined modality treatment have all been employed with limited success. Here we review the existing literature and our own experience with external beam radiation followed by low-dose-rate or high-dose-rate intracavitary radiation for carcinoma of esophagus. The addition of intracavitary brachytherapy to external beam irradiation is well tolerated, causes no significant toxicity, and improves local control. Low-dose-rate intracavitary boost compared to high-dose-rate intracavitary boost has the advantage of a greater margin of safety, requires a single application, does not require highly sophisticated computerized technology, and is accompanied with fewer high-grade toxicities. Combined modality therapy consisting of concomitant infusional chemotherapy, external beam irradiation, and low-dose-rate intracavitary boost needs to be investigated.

Brachytherapy for cancer of the female urethra.

Carcinoma of the female urethra is uncommon. The review of literature and our own experience indicates that early distal urethral cancers (squamous and adenocarcinoma) can be treated either with surgery (70-80% 5-year survival) or with radiotherapy (brachytherapy) with excellent results (75% 5-year survival). Early proximal or entire urethral cancers (squamous and adenocarcinoma), if treated surgically, will require exenterative procedures. Alternatively, these cancers can be treated with a combination of external beam and brachytherapy with or without chemotherapy with good results and preservation of organs. Surgery can be used for failures or persistent tumors. Advanced cancers require a multimodality approach, and a combination of radiation and chemotherapy appears to be the optimal way to treat these patients-with surgery to be used for biopsy-proven persistent tumors or recurrences.

External radiotherapy in macular degeneration: technique and preliminary subjective response.

PURPOSE: This study attempted to assess the toxicity and possible preliminary benefits from the administration of low-dose external beam irradiation for age-related macular degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neovasculature which would result in reabsorption of fluid and blood. This would reduce the risk for further leakage or bleeding, as well as subretinal fibrosis. Consequently, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet ARMD with the possibility for slight improvement. METHODS AND MATERIALS: Allegheny University Department of Radiation Oncology treated 41 patients prospectively from January through October 1995 with low-dose irradiation for wet-type macular degeneration. A total of 39 patients were treated with a total dose of 14.4 Gy in eight fractions of 1.8 Gy/fraction over 10-13 elapsed days. The first two patients were treated with a total dose of 10 Gy in five fractions of 2 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. Some of the patients (36.7%) had laser treatments in the study eye: 21.9% (9) once, 5% (2) twice, 9.7% (4) thrice or more. Subjective visual acuity and toxicity data were collected on all patients. RESULTS: At 2-3 weeks after treatment 29 patients (70%) retained their visual acuity without change, 10 (24.5%) stated they had improved vision, and 2 (4.8%) stated their vision continued to decrease. At 2-3 months after treatment, 27 patients (65.8%) had no change in their vision, 11 (27%) had an improvement in their vision, and 3 (7.2%) had a decrease in visual acuity. Six patients of 41 in the treated group had acute transient side effects. CONCLUSION: Our observations in this group of 41 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age-related wet-type macular degeneration.

Innovations in brachytherapy in gynecologic oncology.

With the discovery of radium by Curie in 1898, researchers recognized that this unique radionuclide had specific biologic properties that were applicable to treating patients with cancer. In the beginning, the radium sources were placed within cavities as independent sources and, when needles were available, implanted into tissues. The first combination of brachytherapy, technologies with external-beam radiation therapy was reported by Wright at the Memorial Sloan-Kettering Cancer Center in New York in 1914 in the treatment of a patient with cervical cancer. Next, there was a rapid implementation of brachytherapy in the treatment of cancer by intracavitary placement of radionuclides, interstitial implantation technologies, and systemic administrations. With the development of new radionuclides, including cesium-137, cobalt-60, iridium-192, iodine-125, palladium-103, ruthenium-109, strontium-90, iodine-131, and californium-225, which had varying types of radiation emissions appropriate when properly selected in treatment of cancer, there was a rapid development of innovative technologies to treat all malignancies, especially gynecologic cancer. The evolution of events brought forth new applicators and techniques that allowed for better distribution of the radiation dosage within the tumor being treated, safer use of radionuclides, and the development of computer programs allowing for varying source applications and dose distributions within the volume implanted.

Cancer of the esophagus following allogeneic bone marrow transplantation for acute leukemia.

The successful development of allogeneic bone marrow transplantation (BMT) has markedly improved the treatment results for acute leukemia and other hematologic diseases. However, significant complications are associated with this procedure including the development of chronic graft versus host disease (GVHD). Treatment for this condition requires chronic immunosuppression which can lead to the development of second cancers. It is well known that immunosuppression is associated with a variety of tumors, most commonly lymphoma. The development of solid tumors appears to be less common but follow-up studies of patients treated for Hodgkin's disease demonstrate a rising incidence of solid tumor development after a delay of 5 to 10 years. We describe a patient recently treated for a squamous cell carcinoma of the esophagus which developed 5 years after an allogeneic BMT for acute myelogenous leukemia (AML). The patient had been treated with immunosuppressants for chronic GVHD. The clinical course is described and the literature is reviewed regarding recent experience with the development of solid tumors following allogeneic BMT. The majority of second tumors following BMT are lymphomas and leukemias. Secondary solid tumors are less common, but the incidence appears to increase over time. Squamous carcinomas are most common and a preparative regimen combining radiation and chemotherapy may increase risk. Careful long-term follow-up of BMT is essential in order to detect second tumors at an early stage.

Heightened sensitivity of the esophagus to radiation in a patient with AIDS.

Esophageal stricture is an uncommon complication in HIV-negative patients treated with radiation to the chest for lung cancer. There have been a number of recent reports on the association of cancer and HIV-positive patients, as well as a greater sensitivity to radiation therapy of the mucous membranes in HIV/AIDS patients. This article reflects a review of the literature on the risk of major complications and morbidity of the esophagus in HIV+/AIDS patients whose chests are treated with radiation for lung cancer. Included is a report of a previously unpublished case of an early and severe esophageal reaction to radiation therapy in an AIDS patient.

Extracorporeal photopheresis and recombinant interferon alfa 2b in Sezary syndrome. Use of dual marker labeling to monitor therapeutic response.

The purpose of this pilot study was to evaluate the role of recombinant interferon alfa 2b (rIFN-a) as adjunct immunomodulatory therapy in patients with Sezary syndrome who were considered unlikely to respond to ExP alone. Six patients were treated with rIFN-a in doses ranging from 3 to 20 million units three times weekly in addition to two consecutive photopheresis treatments every 4 weeks. In addition, to better measure the effect of treatment on circulating neoplastic T-cells, cryopreserved lymphocytes were studied by two-color immunofluorescence and flow cytometry, using anti-CD4 combined with anti-CD29, anti-CD45RA, or anti-CD7. Minimal clinical improvement was observed in 4 patients treated with low doses of rIFN-a (3 to 5 million units TIW), and the response was sustained in only 1 patient. However, a clinically significant and sustained improvement did occur in 1 patient after the dose of rIFN-a was increased (20 million units TIW). Although the encountered toxicity profile from combined ExP/rIFN-a therapy was similar to that expected for ExP or comparable doses of rIFN-a given separately, treatment was discontinued in 2 patients because of adverse effects. Three antibody pairs, i.e., CD4+CD7-, CD4+CD29+, and CD4+CD45RA- subsets, appeared to be useful to monitor changes in blood Sezary cells during treatment. We conclude that the combination of ExP and low doses of rIFN-a does not appear to be effective for patients with advanced Sezary syndrome in this small patient series. However, escalation of interferon dose may be beneficial as shown in one patient, but it cannot be discerned whether the response was due to a combination of therapies, or whether the same therapeutic response would have been achieved with the higher doses of rIFN-a alone. Moreover, while none of the antibody pairs is unique for Sezary cells, the CD4+CD7- subset in appropriate patients provided a good objective measure of response and correlated well with visual Sezary cell counts.

Intracavitary brachytherapy for squamous cell carcinoma of the esophagus.

From September 1983 through January 1989, 8 patients with a diagnosis of squamous cell carcinoma of the esophagus AJCC stages I to III, were treated with intracavitary brachytherapy following external irradiation. Within 3 months after completion of treatment, there was radiographic evidence of complete response in 6 of the 8 patients. None of the responders recurred locally. All the patients have died, with a mean survival of 17 months. One patient died of a stroke 2 1/2 years after completion of treatments without clinical evidence of esophageal cancer. Treatment was well tolerated, with minimal acute toxicity, and one patient developed stricture at the site of tumor, which was successfully treated by dilatation. Addition of systemic chemotherapy to this regimen warrants investigation.

Therapeutic advances in radiologic treatment of cancer.

In 1993, roughly 1,170,000 new cases of invasive cancer will be diagnosed in the United States. A considerable portion of these patients who die will do so because of uncontrolled local and/or regional disease. Numerous advances in the radiologic treatment of cancer have led to improved local and regional control, as well as survival. These advances include improved radiologic imaging techniques, improved techniques of radiation therapy, innovative brachytherapeutic techniques, intraoperative electron beam therapy techniques, and stereotaxic radiosurgical techniques. In this paper, the authors discuss these techniques with specific attention to how they have lead to improved local and regional control, as well as cancer cure with organ preservation.