The present and future role of monoclonal antibodies in the management of cancer. Summary.
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Biomedical subjects
Publications and source records attributed to A M Markoe.
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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.
A review of 1019 patients with posterior uveal melanomas who were treated with episcleral plaque radiotherapy showed that 59 (6%) required enucleation of the affected eye. Seventeen of the enucleations were done within 1 year, 30 within 2 years, and 55 within 5 years. The enucleated eyes had been treated with a cobalt-60 plaque in 39 cases, a ruthenium-106 plaque in 13 cases, an iodine-125 plaque in four cases, and an iridium-192 plaque in three cases. The primary reasons for enucleation included tumor regrowth in 30 cases (51%), neovascular glaucoma in 18 (31%), patient request in five (8%), scleral melting in four (7%), painful bullous keratopathy in one (2%), and hemolytic glaucoma in one (2%). The time interval from plaque treatment to eventual enucleation averaged 29 months. Tumor regrowth requiring enucleation was detected clinically an average of 28 months after treatment. In these cases the average radiation dose to the tumor apex was 7700 cGy and to the tumor base 36,000 cGy. Uncontrollable neovascular glaucoma occurred an average of 38 months after plaque radiotherapy and, most commonly, after cobalt-60 plaques were used. Eyes with plaque-induced scleral melting eventually required enucleation after an average of 10 months. In all cases of scleral melting, the tumor was ciliochoroidal.
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 authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).
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.
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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.
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In 1987, the American Cancer Society has anticipated that 965,000 new cases of invasive cancer will be diagnosed in the United States. About 40% of those patients can be treated for cure with organ preservation using radiation therapy. The basic biologic background for such an approach to the problem has become well established. The clinical data to substantiate the validity of the concept date from 1902 until the present. Organ preservation has become a major and important concept in the management of the patient with invasive cancer. New and innovative techniques for treatment are enabling the organ to be preserved, the cancer to be cured, and appropriate cosmesis and function to be preserved. Many tumor sites are appropriate for this treatment technique, including breast, eye, larynx, prostate, soft tissue sarcomas, etc.
In 1986 73,400 new cases of invasive gynecologic cancer and 45,000 new cases of in situ carcinoma of the uterine cervix (about 9% of all cancers in women) were diagnosed in the US. A significant proportion of these patients die of local failure. In dealing with the wide variety of gynecologic cancers, extreme care must be used in choosing the appropriate treatment program for each problem. Therefore, the full extent of the disease at the time of initial presentation and recurrence must be determined. It is only with these data that appropriate treatment programs can be designed with the maximum potential for long-term control or cure and with the minimum in treatment complication. There are no groups of disease processes like those seen in advanced or recurrent gynecologic cancer that offer such a challenge to the clinical practitioner.
Computed tomographic (CT) scans were obtained from 48 patients with posterior uveal melanoma. The CT measurements of maximal and minimal basal diameters and thickness of each tumor were compared with the assessments of these tumor dimensions obtained by ophthalmoscopic estimation (basal diameters only) and standardized A-scan ultrasonography (thickness only) and with the gross pathologic measurements of these tumors. The correlation between measurements of tumor thickness by CT scanning, standardized A-scan ultrasonography, and gross pathologic analysis was substantially better than that between the CT, ophthalmoscopic, and gross pathologic measurements of tumor basal diameters. Computed tomographic scanning appears to be a good method for determining the in vivo size of choroidal and ciliary body melanomas.
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To determine the prognostic value of the regression rate of choroidal melanomas after cobalt-60 plaque radiotherapy, the authors performed a multivariate analysis on 159 patients treated with a cobalt plaque during the interval from 1976 through 1980. Thirty-three of the 159 patients had died as of the survey date; 29 of metastatic melanoma and 4 of other causes. Multivariate Cox proportional hazards modeling identified a two-term regression incorporating maximal basal tumor diameter at treatment and tumor thickness at 12 months posttreatment as the best model (P less than 0.005 for both parameters) for predicting length of tumor-free survival. These results are consistent with the hypothesis that rapid regression of a choroidal melanoma after cobalt-60 plaque radiotherapy is an unfavorable prognostic sign for prolonged metastasis-free survival.
Of 120 patients with FIGO stage IIA-IVB squamous cell carcinoma of the cervix treated with standard radiotherapeutic techniques, 41 (34.2%) relapsed with hematogenous or serosal metastases. Development of such metastases was individually associated with patient age less than or equal to 55, bilateral bulky parametrial extension, and histologically positive paraaortic nodes. Poor histologic differentiation exerted significant negative influence only in patients age less than or equal to 55. Neither surgical staging nor vascular injury predisposed to hematogenous dissemination. Radiotherapy techniques differed only in increased time to completion, from 84 to 100 days in clinical IIB and IIIB patients developing metastases. Local or regional pelvic recurrences, although associated with an increase in hematogenous or serosal metastases, were not accompanied by concomitant relapse in extrapelvic nodes. Twenty-six of 41 metastases were limited to single organ systems, with pulmonary sites most common (43.9%). A direct (non-nodal) route of hematogenous dissemination of 31% was documented within clinical stages IIA and IIB. One hundred percent concordance between bilateral bulky parametrial involvement and positive pretreatment paraaortic nodes occurred in clinical stage IIIB and IVA patients with metastatic relapse. Our data from the period 1976-1985 do not substantially differ from earlier reports on the incidence or distribution of hematogenous or serosal metastases, despite our implementation of contemporary local/regional radiotherapy prescriptions. The potential for hematogenous and serosal metastases in high-risk patients with advanced squamous cervical carcinoma merits consideration of alternative treatment protocols and precise definition of the role of pretreatment surgical staging procedures.
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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.