Brain metastases in renal cell carcinoma: management with gamma knife radiosurgery.

PURPOSE: The purpose of this study was to evaluate survival and local control of brain metastases in patients with renal cell carcinoma. METHODS AND MATERIALS: From November 1993 through March 1999, 38 radiosurgical treatments using the Leksell gamma knife unit were performed on 22 patients with renal cell carcinoma. The indications for treatment were failure after whole-brain radiation therapy or de novo treatment. All radiosurgical treatments were given on an outpatient basis. The workup included computed tomography and magnetic resonance imaging. The age of the patients ranged from 38 to 80 years (median age, 60 years). The mean minimum tumor dose was 18 Gy, and the mean volume was 3.9 cc. Previous whole-brain radiation therapy was used in 11/22 (50%) patients. Four of 22 patients presented with single metastasis. Thirteen patients were treated once, one patient was treated four times and one patient seven times for new lesions. The number of lesions treated ranged from one to 21. RESULTS: One patient is al ive at 63 months of fol low-up. Twenty-one patients died, with a median survival of 8 months (range, 1-38 months). Eighteen of 21 patients died of nonneurologic causes. Overall local control was 98.5%. One patient developed radiation necrosis. CONCLUSIONS The long-term survival achieved in patients with renal cell carcinoma requires aggressive management, even in the presence of multiple brain metastases. Gamma knife radiosurgery for renal cell carcinoma is an effective noninvasive modality of treatment. It offers high local control rate and improved quality of life and survival.

Gamma knife radiosurgery in the treatment of patients with single and multiple brain metastases from carcinoma of the breast.

PURPOSE: The purpose of the study was to evaluate the results of gamma knife radiosurgery for treatment of brain metastases from carcinoma of the breast. MATERIALS AND METHODS: From December 1993 to July 1998, 68 women with breast carcinoma metastatic to the brain were treated with gamma knife radiosurgery at Miami Neuroscience Center in Coral Gables, Florida. The ages ranged from 25 to 80 years, with a median age of 52 years. Thirty-eight patients had previously received conventional modalities of treatment for brain metastases including whole-brain irradiation. A total of 110 treatments were given to the 68 women to an average of eight tumor sites per patient. Minimum doses ranged from 6 to 25 Gy to the 35% to 85% isodose line, with 95% of the prescribed minimum doses ranging from 15 to 24 Gy. Patients were treated for one to three lesions (n = 26), four to seven lesions (n = 18), and eight or more lesions (n = 24). RESULTS: The median overall actuarial survival for the entire group was 7.8 months. The actuarial survival was 32% at 1 year. The median follow-up was 7.8 months. Overall local control by lesion was 94% (485/518 lesions), and average tumor volume was 3.3 cm3. Twenty-seven (40%) of 68 eligible patients survived 1 year, nine (13%) survived 2 years, and two (3%) survived more than 3 years. Fifty-one of 56 documented deaths (91%) were unrelated to brain metastases. In a subgroup of 15 patients with single brain metastases, the average tumor volume was 16.6 cm3, and local control was 73% (11/15 lesions). The 15 patients who died had a median survival of 7.7 months (range, 3 to 45.7 months). CONCLUSIONS: Gamma knife radiosurgical treatment of patients with brain metastases from carcinoma of the breast has shifted the question of survival to that of systemic control. There was no radiation-induced dementia, and a remarkably low incidence of local failure was seen. Survival has been found to be independent of the number of lesions treated.

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

Radiotherapy of retinoblastoma. A review of 63 children treated with different irradiation techniques.

This is a retrospective review of treatment results in 63 children with retinoblastoma (RB) who received therapeutic irradiation from January 1975 to June 1988. Patient ages ranged from birth to 5 years with a mean age of 12.5 months. Three treatment groups were identified. In Group A, episcleral plaque was the only irradiation modality. In this group, 24 patients and 25 eyes with tumors of Reese-Ellsworth Stages I to III, and selected Stage VB tumors were irradiated using eye plaques. Twenty-two of 25 (88%) eyes are without evidence of disease (NED), and all patients are alive. Two eyes were enucleated for recurrent RB. Two of 23 eyes developed minimal cataracts. In Group B, external-beam was the only irradiation modality. Twelve patients with 21 involved eyes comprise this group. Thirteen eyes received EBRT alone. Seventy-seven percent of 13 eyes have NED. Four eyes developed cataracts. Three of 13 eyes required enucleation for progression of disease; one of these was Stage IVA and two of them were Stage VA. For Group C, external-beam plus episcleral plaque was used. Twenty-seven patients and 51 eyes with advanced retinoblastoma were included in this group. Episcleral plaque was used in 29 eyes as a salvage procedure for recurrent RB, or in selected cases was used as a boost after initial external beam irradiation. Fifteen of 29 eyes (52%) remain with NED with useful vision, and nine developed cataracts. Enucleation was performed in 14 eyes for recurrent RB. The authors conclude that radiation therapy has a major role in the management of RB due to its ability to control even advanced disease, allowing preservation of vision in a significant number of patients.

Monoclonal antibodies in the treatment of metastatic carcinoma to the liver: report of a pilot study including leukopheresis.

Thirteen patients with metastatic liver carcinoma were treated with hepatic irradiation, leukopheresis and monoclonal antibodies to test the tumoricidal effects of murine 17-1A immunoglobulin G (IgG) Mab. A significant increase in survival for this group of patients was identified.

Recurrent pterygia: results of postoperative treatment with Sr-90 applicators.

Recurrent pterygia in 42 patients (48 eyes) were treated locally with strontium-90 irradiation from May 1967 to May 1988. The 31 male patients had an average age of 52 years; the 11 female patients, 46 years. All patients underwent surgical resection of the recurrent pterygia with use of the bare-sclera technique. During the immediate postoperative period the surgical site was treated with an Sr-90 applicator (beta irradiation). Doses ranged from 10 to 70 Gy (average, 50 Gy). Follow-up times ranged from 8 to 136 months (median, 14 months). The local control rate was 89%. Four of the five recurrences were in patients treated with doses of 1,000-1,500 cGy (P less than .0002). None of the patients developed cataracts or any other serious complications.

Lymphoma of the thyroid. Report of five cases and review.

Thyroid lymphoma is a rare disease seen most commonly in elderly women and associated with Hashimoto's thyroiditis. Five cases of thyroid lymphoma seen and treated at Hahnemann University Hospital between 1979 and 1988 are retrospectively reviewed. All patients underwent a staging workup, including chest radiograph, intravenous pyelography, abdominal/pelvic computed tomogram (CT) scan and/or lymphangiogram, and bone marrow. An extensive review of the literature is presented. Risk factors for thyroid lymphoma are discussed, enabling the clinician to differentiate thyroid lymphoma from thyroid carcinoma. Thyroidectomy may be indicated in a small number of cases, provided that the patient has disease localized within the thyroid such that total gross resection can be achieved. It is proposed that patients with bad prognostic factors may benefit from the administration of chemotherapy initially before or after radiotherapy rather than using chemotherapy as salvage therapy. Irradiating the patient to the neck and mediastinum to 40 Gy, in 4-5 weeks, is recommended, except possibly for tumor that is extremely well localized in the neck. Finally, the necessity of a full staging work-up, including lymphangiogram and/or abdominal/pelvic CT is emphasized.

Superficial chest wall recurrences of breast cancer: prognostic treatment factors for combined radiation therapy and hyperthermia.

Forty-nine patients with chest wall recurrences of breast carcinoma received radiation therapy and 915-MHz microwave hyperthermia for 95 lesions. Follow-up ranged from 3 to 39 months, with five patients dying before 6 months follow-up. At 1 month follow-up, 49 (52%) of 95 lesions showed complete response; 28 (29%), partial response; and 18 (19%), no change. At 6 or more months follow-up, 54 (67%) of 81 lesions demonstrated local control; 10 (12%), partial response; six (7%), no change; and 11 (14%), local-regional recurrences. Superficial blisters occurred in 24 (25%) of 95 lesions, whereas long-term complications (deep necrosis, subcutaneous burns) occurred in seven (7%) lesions. Relapse occurred in 16 (17%) lesions, seven after initial complete response and nine after partial response. Several prognostic treatment factors were identified: applied radiation dose (greater than 30 Gy, P less than .01), size of tumor (less than 6 cm diameter, P less than .001), minimum tumor temperature (greater than 41 degrees C, P less than .001), and status of disease (M0 or M1 vs M2, P less than .001). Treatment complications were correlated with maximum temperatures (greater than 45 degrees C, P less than .001). In summary the palliative treatment concept proved to be safe and effective.

Radiation-associated sarcoma: a review of 23 patients with postradiation sarcoma over a 50-year period.

Between 1934 and 1983, 23 patients with well-documented diagnosis of radiation-associated sarcoma (RAS) were seen at the University of Michigan Medical Center. The median latent period from irradiation to diagnosis of RAS was 13 years with a minimum latent period of 3 and a maximum of 34 years. All sarcomas originated in previously normal tissues within the irradiated field. Pathology slides available in all patients were reviewed by the same pathologist for the purpose of the study, and the diagnosis of sarcoma was confirmed histologically. There were five bone sarcomas and 18 soft tissue sarcomas. Thirteen patients developed radiation-associated sarcoma following megavoltage treatment with a minimum total radiation dose of 25 Gy in 2 1/2 weeks. The other 10 patients received orthovoltage and/or brachytherapy irradiation alone or combined with external beam radiation. In this group, the radiation doses ranged from 25 Gy to 72 Gy except for one patient who received 8 Gy delivered by orthovoltage irradiation as treatment of knee arthritis. Four patients were originally treated for benign conditions. All the other patients (n = 19) received radiation therapy for a variety of primary malignancies including carcinoma of the cervix (n = 4), brain gliomas (n = 13), Wilm's tumors (n = 2) and retinoblastomas (n = 2), among others.

Analysis of treatment results in 36 children with retinoblastoma treated by scleral plaque irradiation.

This is a retrospective analysis of treatment results in 36 patients with retinoblastoma treated by the Radiation Oncology Department of Hahnemann University Hospital and the Division of Oncology of Wills Eye Hospital between January 1975 and December 1986. There were 14 females and 22 males; ages ranged from 2 months to 4 1/2 years of age at presentation. Leukocoria was the most common clinical sign of presentation. These patients were treated with external beam radiation therapy in combination with scleral plaque irradiation in 20 patients and with scleral plaque alone in 16 patients. Cobalt-60, Iodine-125, Iridium-192, and Ruthenium-106, scleral plaques were used. The dose delivered to the mid plane of the globe was 40 Gy and the scleral dose adjacent to the plaque was in the range of 180-200 Gy. The treatment was successful in 30 of 36 patients. Complications of radiation therapy were minimal in patients treated by scleral plaque alone. The advantages of this treatment modality are discussed.

Episcleral plaque radiotherapy for retinoblastoma.

The authors report their preliminary results of episcleral plaque radiotherapy (cobalt 60, iridium 192, ruthenium 106, and iodine 125 plaques) in 50 selected patients with retinoblastoma. There were 97 plaque applications to 51 affected eyes in these 50 patients. The plaque was used as primary treatment in 15 eyes and as secondary treatment after failure of external beam radiotherapy, photocoagulation, and/or cryotherapy in 36 eyes. Vitreous seeding of tumor cells was evident ophthalmoscopically in 49 of the 51 eyes, negating the possibility of ultimate success by further photocoagulation or cryotherapy. In 18 patients, the contralateral eye had been enucleated and the remaining eye was being considered for enucleation because all other treatment modalities had failed. In 2 of these 18 patients (11%), the remaining eye was salvaged with plaque radiotherapy and some vision was preserved. In 33 eyes with less advanced tumors, 31 had some degree of vitreous seeding by tumor cells. The eye has been retained in all 33 of these patients and useful vision preserved in most. On the basis of these preliminary observations, the authors conclude that plaque radiotherapy can be used successfully as a primary treatment for selected cases of unilateral or bilateral retinoblastoma or as a supplemental treatment after other treatment methods have failed. The current indications for plaque radiotherapy and its advantages over other therapeutic modalities are discussed.

The treatment of primary intraocular malignancy.

This paper will summarize much of the information derived in an association between The Department of Radiation Oncology of Hahnemann University Hospital and the Oncology Service of Wills Eye Hospital of Thomas Jefferson University, a collaborative effort for the treatment of primary intraocular malignancies that has spanned the last dozen years. In that time we have treated malignant intraocular melanoma by radioactive eyeplaque brachytherapy and have begun to develop a similar program for treatment of recurring retinoblastoma. These experiences will be described.

Isolated testicular leukemic relapse. Response to radiation therapy.

Between January, 1975, and December, 1984, at the University of Michigan Medical Center, 17 boys with leukemia presented with overt or occult isolated testicular relapse. Diagnosis was obtained by bilateral open-wedge biopsies of the testes. All the patients were treated with combined local testicular irradiation and systemic chemotherapy. In only 1 of the 17 patients (6%) testicular leukemia developed as the only site of relapse. It appears that doses in the range of 2,000 to 2,400 cGy in 10 to 12 fractions achieve optimum control of leukemic infiltration of the testes.

Clinical treatment planning in gynecologic cancer.

Treatment planning in gynecologic cancer is a complicated and difficult procedure. It requires an adequate preoperative assessment of the true extent of the patient's disease process and oftentimes this can be achieved not only by conventional studies but must employ surgical exploratory techniques in order to truly define the extent of the disease. However, with contemporary sophisticated treatment planning techniques that are now available in most contemporary departments of radiation oncology, radiation therapy is reemerging as an important and major treatment technique in the management of patients with gynecologic cancer.

Primary large-cell lymphoma of the central nervous system.

Primary non-Hodgkin's lymphoma of the central nervous system (CNS) is a rare disease. Seven patients were seen and treated at the University of Michigan Medical Center between January 1969 and December 1983. All patients had histologically proven diagnoses of large cell lymphoma with clinical and radiologic evidence of involvement limited to the CNS. Five of seven patients received postoperative radiation therapy, two of whom have had apparent local control at 1- and 2-year follow-up. The two patients without postoperative radiation died of local recurrence 2 and 3 months following subtotal resection. These poor results suggest that adjuvant therapy may be required for improved control of this type of extranodal lymphoma.

Chordoma: role of radiation therapy.

The treatment of 21 patients with a diagnosis of chordoma seen over a 20-year period is described. The 13 men and eight women (ratio 1.6:1) ranged in age from 7 to 82 years (average, 50 years). Eleven chordomas arose from the clivus; the others originated in the sacral region (three patients), thoracic spine (one), cervical spine (three), and lumbar spine (three). Primary treatment consisted of surgery, reserving radiation therapy for recurrence in the majority of patients. Radiation doses, delivered with megavoltage equipment, ranged between 5,000 cGy delivered over 5 weeks and 6,600 cGy over 6 1/2 weeks. Irradiation produced significant tumor control, with remission of symptoms from 1 to 6 years. The combination of high-dose radiation therapy and complete or subtotal surgical resection offers the best chance for prolonged survival in this group of patients.

Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children's Cancer Study Group.

A retrospective review of all 115 infants less than 1 year of age with acute lymphoblastic leukemia (ALL) entered on a consecutive series of recent Children's Cancer Study Group (CCSG) leukemia protocols was undertaken to examine in detail the outcome and clinical course of a large group of similarly treated infants. In comparison to the 4,392 children older than 1 year, entered on the same studies, infants had a significantly (P = .0001) increased incidence of leukocytosis, hepatosplenomegaly, meningeal leukemia at presentation, hypogammaglobulinemia, and failure to achieve complete remission (CR) status by day 14 of induction therapy. In contrast, lymphadenopathy, non-L1 French-American-British (FAB) morphology, mediastinal mass, and T cell leukemia were not more frequently observed. Ninety percent of these infants successfully completed the induction phase of therapy. With a median follow-up of 35 months, life table estimate of disease-free survival is only 23% at 4 years. Identical disease-free survival rates for infants were observed in each of the individual studies reviewed. Excessive toxicity resulting in limitation of therapy delivered was not a causative factor for the disappointing outcome of these patients. Rather, early disease recurrence, characterized by bone marrow relapse (55%) and CNS (22%) relapse, was the major factor responsible for the extremely poor prognosis of this patient group. Identical CNS relapse rates were observed in those patients who received cranial irradiation as part of CNS prophylaxis (21.8%) and in those patients who did not receive cranial radiotherapy (24%). Results of salvage therapy for patients who experienced systemic or extramedullary relapse were dismal. Debilitating neuropsychologic sequellae, presumably related to CNS irradiation, have been observed in 50% of the small number of long-term survivors. Infants less than 1 year of age with ALL present with a constellation of features which predict a poor outcome and constitute the group of children with ALL at greatest risk for treatment failure.