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Biomedical subjects

A M Markoe

Publications and source records attributed to A M Markoe.

At least 19 recordsLinked to original sources

The prognostic significance of surgical staging for carcinoma of the endometrium.

This study is based on a retrospective review of 156 patients with endometrial carcinoma from 1978 through 1984 who underwent primary surgical evaluation. All cases were retrospectively restaged using the newly adopted FIGO surgical staging. The preoperative FIGO clinical stage distribution for this study was as follows: 121 (77.6%) Stage I, 22 (14.1%) Stage II, 5 (3.2%) Stage III, 2 (1.3%) Stage IV, and 6 (3.8%) unstaged patients. Most patients had TAH-BSO with a collection of peritoneal washings and retroperitoneal lymph node sampling. Surgical staging revealed 122 (78.2%) Stage I, 9 (5.8%) Stage II, 12 (7.7%) Stage III, and 13 (8.3%) Stage IV patients. Surgery upstaged 12.4% of clinical Stage I. In clinical stage II, 59.0% were downstaged while 27.3% were upstaged. For clinical Stage III, 60.6% were upstaged, but no downstaging occurred. No change in stage occurred for clinical Stage IV patients. Ninety-seven surgically staged patients received no adjuvant therapy. The remaining 59 patients had adjunctive treatment which consisted of radiotherapy (59.3%), hormonal therapy (25.4%), chemotherapy (5.1%), or combined modality treatment (10.2%). All patients were followed until death or a minimum of 5 years (60-139 months; median, 82 months) with the exception of 13 patients who were lost to follow-up (2-58 months; median, 34 months). Five-year survival by clinical staging was as follows: 86.2% for Stage I, 85.9% for Stage II, and 0% for Stage III and IV. Five-year survival by surgical staging was 90.6% for Stage I, 85.7% for Stage II, 58.3% for Stage III, and 0% for Stage IV. The 13 patients who were lost to follow-up were censored in all survival analyses at the time of last contact. Stepwise regression analysis using a parametric proportional hazards model identified surgical stage as the most significant prognostic factor (P = 0.02). Univariate analysis showed that patients with surgical Stage IC had significantly worse prognosis (75.0%, 5 years) than those in surgical Stage IA (93.8% 5 YS) or IB (95.4% 5 years). In summary, this study demonstrates that surgical staging as recommended by FIGO is indicated to accurately determine the initial extent of disease in endometrial carcinoma. In addition, surgical staging is the strongest predictor of survival. Deep myometrial invasion appears to be a significant independent prognostic factor within surgical Stage I. The role of adjunctive radiotherapy in Stage I disease awaits the results from an ongoing multi-institutional, prospectively randomized trial.

Adenocarcinoma

Dose determination in high dose-rate brachytherapy.

Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (< 1%), depending on the prescribed dose, source activity, and source speed as defined by the implant geometry.

Brachytherapy

Computer controlled stereotaxic radiotherapy system.

A computer-controlled stereotaxic radiotherapy system based on a low-frequency magnetic field technology integrated with a single fixation point stereotaxic guide has been designed and instituted. The magnetic field, generated in space by a special field source located in the accelerator gantry, is digitized in real time by a field sensor that is six degree-of-freedom measurement device. As this sensor is an integral part of the patient stereotaxic halo, the patient position (x, y, z) and orientation (azimuth, elevation, roll) within the accelerator frame of reference are always known. Six parameters--three coordinates and three Euler space angles--are continuously transmitted to a computer where they are analyzed and compared with the stereotaxic parameters of the target point. Hence, the system facilitates rapid and accurate patient set-up for stereotaxic treatment as well as monitoring of patient during the subsequent irradiation session. The stereotaxic system has been developed to promote the integration of diagnostic and therapeutic procedures, with the specific aim of integrating CT and/or MR aided tumor localization and long term (4- to 7-week) fractionated radiotherapy of small intracranial and ocular lesions.

Electromagnetic Phenomena

Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study.

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.

Adult

Optimization of high dose-rate cervix brachytherapy; Part I: Dose distribution.

Computer controlled high dose-rate (HDR) brachytherapy afterloading machines are equipped with a single, miniaturized, high activity Ir-192 source that can be rapidly moved in fine increments among several channels. Consequently, by appropriate programming of source dwell positions and times, the dose distribution can be optimized as desired. We have explored the optimization potential of this new technology for two applications: (a) cervix brachytherapy, and (b) transvaginal irradiation. Cervix brachytherapy with a gynecologic ring applicator was simulated by 48 sources of relative activities ranging from 0.17 to 1.00 that were equally distributed between the tandem and the ring. The results confirmed that the optimized distribution of physical doses are superior to those achievable with standard brachytherapy sources and applicators. For example, with five-point optimization, the relative dose-rate in the rectum was only 47% of that in point A; for standard application the dose rate was 47% higher. For transvaginal application 27 sources of relative activities between 0.07-0.79 were placed in the ring and a single source of unit strength in the tandem. Using dose distribution homogeneity as an optimization criterion, the results (+/- 2.5%) were again superior to those obtained for commonly used double ovoid (+/- 15%), linear cylinder (+/- 27%), or a "T" source (31%).

Brachytherapy

Radiation therapy for adjunctive treatment of adrenal cortical carcinoma.

Adrenocortical carcinoma is a rare disease which is primarily approached surgically. There have been few reports of the efficacy of radiation therapy and, for the most part, these have been anecdotal. This paper reports on the potential adjuvant role of radiation therapy after surgical excision of primary adrenal cortical carcinoma and also comments about the efficacy of palliative radiation therapy for metastases. We have identified eight patients treated for adrenal cortical carcinomas at Hahnemann University Hospital (HUH) from 1962 until the present and have also identified five patients with the same diagnosis at Philadelphia General Hospital (PGH) from 1962 until its close in 1975. These two groups are examined separately. In the PGH group, in which two patients were diagnosed at autopsy and only one patient was treated by radiation therapy, the median survival was between 0 and 1 month for Stage IV disease with the only patient surviving to 6 months being that patient receiving radiation therapy. In the HUH group, five of eight patients were treated adjunctively after diagnosis, one was not and two received palliative therapy. The median survival for treated Stage III patients was between 34 months and 7 years. The suggestion, based on a limited patient series, is that patients treated postoperatively to the tumor bed and nodal areas in Stage III disease may have improved survival over historic series and improved local control.

Adrenal Gland Neoplasms

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.

Cataract

Innovative techniques in radiation oncology. Clinical research programs to improve local and regional control in cancer.

There is a growing importance in failure analysis in cancer management. In these analyses locoregional failure as the cause of death emerges as a significant problem in many tumor sites, e.g., head and neck cancer, gynecologic cancer, genitourinary cancer. Because of these data, the radiation oncology community has attributed high priority to research efforts to improve locoregional control. These efforts include the following: (1) brachytherapy alone or with external beam radiation therapy or surgery; (2) intraoperative radiation therapy; (3) hyperthermia with radiation therapy; (4) particle irradiation (protons, neutrons, stripped nuclei, and pions); and (5) routes of administration of the treatment, including infusional (intravenous) chemotherapy with radiation therapy, intraarterial monoclonal antibodies with radionuclides, and intraarterial chemotherapy with radiation therapy. Each area of investigation is discussed.

Antineoplastic Combined Chemotherapy Protocols

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.

Bone Neoplasms

Reasons for enucleation after plaque radiotherapy for posterior uveal melanoma. Clinical findings.

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.

Adult

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.

Brachytherapy

Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy.

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%).

Adult

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.

Adult