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Biomedical subjects

R B Marcus

Publications and source records attributed to R B Marcus.

18 recordsLinked to original sources

Pulmonary function tests after whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma.

PURPOSE: Because of the scarcity of information regarding long-term follow-up of pulmonary function after whole-lung irradiation, a prospective study was started at the University of Florida in 1979 to evaluate pulmonary function after treatment with whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. PATIENTS AND METHODS: Between 1979 and 1984, 57 osteogenic sarcoma patients with no evidence of metastatic disease at diagnosis received adjuvant therapy consisting of whole-lung irradiation (with the heart shielded) followed by Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). The whole-lung irradiation schema was 1,600 cGy in 10 fractions with 8-MV x-rays via anterior and posterior fields. This was followed by five cycles of Adriamycin for a total dose of 450 mg/m2. Pulmonary function tests (PFTs) consisting of spirometry, lung volumes, and diffusing capacity were obtained before the whole-lung irradiation, at 6 and 12 months after irradiation, and at yearly intervals thereafter. RESULTS: At the time of analysis, 28 of the 57 patients were available for study, with a mean follow-up of 42 months (range, 6 to 77 months). Follow-up pulmonary function testing revealed decreased forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) during the first 6 to 12 months after whole-lung irradiation. These values returned to baseline during the second-year posttherapy and remained at baseline throughout the remainder of the follow-up period. Changes in lung volumes demonstrated a similar early trend, with significant decreases in total lung capacity (TLC) and functional residual capacity (FRC) at 6 to 12 months. These changes, however, did not improve significantly during the remainder of the follow-up period. Diffusing capacity of the lungs for carbon monoxide (DLCO) also reached a nadir at 6 to 12 months after whole-lung irradiation, with resolution by 2 years and maintenance of at least baseline values for the remainder of the follow-up period. CONCLUSIONS: Treatment with whole-lung irradiation and Adriamycin, as given in this study, caused no significant sequelae, as demonstrated by pulmonary function testing during the mean follow-up period of 42 months, although a mild, transient restrictive ventilatory defect occurred at 6 to 12 months after treatment.

Adolescent

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease.

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.

Adolescent

Local control and function after twice-a-day radiotherapy for Ewing's sarcoma of bone.

Between February 1982 and December 1987, 39 patients with Ewing's sarcoma of bone have been treated at the University of Florida with a twice-a-day radiotherapy regimen to their primary lesion, 35 with radiation alone and 4 with a combination of radiation and surgery. Although three separate systemic regimens were used (standard risk, 1982-1987 [SR-1]; high-risk, 1982-1984 [HR-2]; and high-risk, 1985-1987 [HR-3]), the radiotherapy regimen remained constant through the years of the study. Those patients whose soft-tissue mass completely regressed after induction chemotherapy received 5040 cGy (as did patients with no soft-tissue mass at diagnosis), those who had 50% or greater resolution of the soft-tissue mass received 5520 cGy, and those who had less than 50% regression of the soft-tissue mass or progressive disease during induction chemotherapy received 6000 cGy. All patients were treated with 120 cGy twice a day and a 6-hr separation between fractions. Thirteen patients also received 800 cGy of total body radiotherapy (TBI) 1 to 3 months after local radiotherapy as part of their systemic treatment. In the 33 patients treated with radiotherapy alone who were eligible for local control analysis, there have been three local failures to date, all within the first 21 months after diagnosis. The 5-year local control rate was 88% for SR-1, 80% for HR-2, and 92% for HR-3. Local control was not related to total dose, but by design, the patients with the largest lesions and the poorest response to chemotherapy had the highest doses. In the 20 patients presenting with extremity primary lesions, there have been no pathologic fractures. In patients evaluated for limb function, the late effects have been minimal. The twice-a-day regimen used appears to produce good local control rates with improved long-term function as compared with once-a-day regimens.

Bone Neoplasms

Long-term follow-up of radiotherapy for pituitary adenoma: the absence of late recurrence after greater than or equal to 4500 cGy.

Recent literature has suggested that late recurrence of pituitary adenoma after radiotherapy is common. We hypothesized that late failures might be a result of inadequate dose (less than 4500 cGy). To investigate, we analyzed 105 patients treated at our institution between 1965 and 1986 (analysis, 2/89). The minimum observation time was greater than or equal to 5 years in 58% and greater than or equal to 10 years in 30% of the patients. All patients received megavoltage radiotherapy (range, 4200-5500 cGy; mean, 4821 cGy) at a mean dose per fraction of 172 cGy; 100 patients received greater than or equal to 4500 cGy tumor dose. Twenty-nine patients received radiotherapy alone, and 76 had postoperative radiotherapy after frontal craniotomy (20 patients) or transsphenoidal hypophysectomy (56 patients). At presentation, 71% of patients had extrasellar disease, 57% had visual field deficits, and 50% had endocrinopathy. Of patients treated postoperatively, 74% had gross residual disease. Four local failures occurred at 13, 16, 57, and 64 months after postoperative radiotherapy, all within the irradiated volume (tumor doses of 4700, 4715, 5000, and 5100 cGy). All four patients had presented with moderate to extensive extrasellar disease with visual field defects. Two of the four remain free of second recurrence at 7 and 13 years after salvage transsphenoidal hypophysectomy. The local control rate with radiotherapy (product-limit method) at 10 years was 100% in the radiotherapy-alone group and 92% in the postoperative radiotherapy group (95% for all patients). To prevent bias, seven patients who received bromocriptine, none of whom demonstrated a recurrence, were censored from the local control analysis at the initiation of the drug. No patient in this study suffered recurrence greater than 64 months after radiotherapy, with 31 patients (none with bromocriptine) observed 10 to 21 years. We conclude that treatment of pituitary adenoma with greater than or equal to 4500 cGy in 25 fractions can result in a high (greater than or equal to 90%) probability of stable long-term control.

Adenoma

Late follow-up of a short-term intensive regimen for Ewing's sarcoma.

Twenty-two patients received a short-term intensive regimen for Ewing's sarcoma between November 1977 and December 1981. The regimen consisted of vincristine (1.5 mg/m2) on day 1, and doxorubicin HCl (75 mg/m2) plus cyclophosphamide (1,000 mg/m2) on day 2. Six cycles were given at 28-day intervals. Local irradiation was started shortly after cycle 2. Eight patients with lesions of expendable bones also underwent surgery as part of the treatment to the primary site, 4 at the end of chemotherapy and 4 at diagnosis. The 5-year event-free survival rate was 45% for all patients and 48% for those with localized disease at diagnosis. Two patients died of treatment-related toxicity. The most common form of failure was distant metastases, indicating that finding a better systemic treatment remains the problem in eradicating Ewing's sarcoma.

Adolescent

Preoperative irradiation for soft tissue sarcomas of the trunk and extremities in adults.

Between May 1978 and January 1987, 58 adult patients with previously untreated sarcomas of the trunk and extremities were treated with preoperative irradiation and surgery at the University of Florida. All patients had a minimum of 2 years of follow-up; 24 had a minimum of 5 years of follow-up. The preoperative dose was usually 5040 cGy, with 120-125 cGy per fraction delivered twice daily. Operations were performed 2 to 6 weeks after radiation therapy. Eight patients received adjuvant chemotherapy. The tumors were high grade in 52 (90%), measured greater than 10 cm in 45 (78%), and were extracompartmental in 49 (84%). The surgical margins were wide in 17, marginal in 31, and intralesional in 10 patients. A functional extremity was preserved in 47 of 54 patients who would have required an amputation had they been treated by operation alone. Five of 58 patients (9%) developed local failure; in three, the failure occurred outside of the irradiated volume. Survival rates (product-limit method) at 5 years according to grade and size of lesion were as follows: low grade, 100%; high grade, 10 cm or less in largest diameter, 68%; high grade, 11-20 cm, 39%. Data are insufficient for a 5-year analysis of high-grade lesions greater than 20 cm; to date, there are no 5-year survivors in these patients. Moderate and severe wound complications occurred in 16%. There were four pathological fractures in 52 long bones at risk.

Abdomen

The incidence of myelitis after irradiation of the cervical spinal cord.

To further define the tolerance of the cervical spinal cord, the dose of radiation to the cervical spinal cord was calculated for all 2901 patients with malignancies of the upper respiratory tract treated at the University of Florida between October 1964 and December 1987. To further define the population evaluated, certain criteria were used: (a) a minimum of 3000 cGy to at least 2 cm of cervical spinal cord and (b) a minimum of 1 year of follow-up, unless a neurological complication occurred before 1 year. A total of 1112 patients were evaluable, of which 2 (0.18%) developed radiation myelitis. One received 4658 cGy to the cervical cord at 172.5 cGy per day, and the other patient received 4907 cGy to the cord at 169.2 cGy per day. The risk of myelitis at each dose level was 0/124 at 3000-3999 cGy, 0/442 at 4000-4499 cGy, 2/471 at 4500-4999 cGy, and 0/75 at a cord dose of 5000 cGy or greater.

Dose-Response Relationship, Radiation

Clinical stage I and II endometrial carcinoma treated with surgery and/or radiation therapy: analysis of prognostic and treatment-related factors.

This is an analysis of 266 patients with clinical stage I and II endometrial carcinoma treated with curative intent at the University of Florida between October 1964 and December 1980. There was a minimum 5-year follow-up. Thirty-nine patients who died of intercurrent disease less than 5 years from treatment were excluded from analysis of pelvic disease control and determinate disease-free survival. All patients were included in the analysis of complications. Pelvic disease control and determinate disease-free survival rates at 5 years were 91 and 88%, respectively, for stage I and 84 and 68% for stage II. There was no apparent difference in the rates of local control and survival or in the incidence of complications when comparing preoperative with postoperative radiation therapy. Tumor grade, stage, depth of myometrial invasion, and history of exogenous estrogen use or abnormal estrogen balance were of prognostic significance. Data on pelvic disease control, survival, and treatment complications are outlined, and management guidelines are discussed.

Adenocarcinoma

High-risk Ewing's sarcoma: end-intensification using autologous bone marrow transplantation.

Because of retrospective analysis showing survival to be related to primary tumor size, in February 1982 a study to test this hypothesis prospectively was begun at the University of Florida. Patients with primary tumors 8 cm or less in maximum diameter and no metastases received adjuvant chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, and dactinomycin plus radiotherapy or surgery (standard-risk protocol). All others received a similar regimen followed by end-intensification with high-dose melphalan and autologous bone marrow transplantation (Protocol HR-2). Because of poor results of HR-2, another high-risk protocol (HR-3) was initiated in January 1985. Patients on HR-3 received 2 cycles of chemotherapy containing vincristine, cyclophosphamide, and doxorubicin followed by local radiation therapy and maintenance chemotherapy. At the end of this therapy, autologous bone marrow transplantation (ABMT) was performed, using a preparatory regimen of total body irradiation and intensive chemotherapy. The 2-year disease-free survival rate was 70% for the standard-risk protocol, 20% for HR-2, and 80% for HR-3. The follow-up on HR-3 is still short, but the results are promising enough to warrant further clinical trials.

Antineoplastic Combined Chemotherapy Protocols

The meningioma controversy: postoperative radiation therapy.

Total surgical excision is the main goal of therapy for intracranial meningiomas. The controversy today involves the efficacy of postoperative radiation therapy. To evaluate this question, 132 patients with benign intracranial meningiomas, treated between October 1964 and April 1985, were evaluated. All patients had a minimum 2-year follow-up. The actuarial local control rates at 10 years for the three treatment groups were as follows: subtotal excision alone, 18%; subtotal excision plus postoperative radiation therapy, 82%; and total excision alone, 77%. The actuarial determinate survival rates at 10 years were 49%, 81%, and 93%, respectively. Postoperative radiation therapy was also effective for patients treated at the time of the first recurrence, with an actuarial local control rate at 10 years after salvage treatment of 30% for patients treated with surgery alone and 89% for patients receiving postoperative radiation therapy at the time of salvage. This analysis suggests that radiation therapy has a significant role in the treatment of subtotally excised and recurrent intracranial meningiomas.

Brain Neoplasms

Surgical treatment for osteosarcoma.

Fifty-three patients who had a high-grade osteosarcoma had either a limb-salvage resection or an amputation. They all received adjuvant therapy that consisted of administration of Adriamycin (doxorubicin) and whole-lung irradiation. At the time of follow-up, the surgical margin was assessed by examination of the surgical specimen. Each patient was followed for at least three years or until death. The data suggested that a wide surgical margin is adequate to control a primary osteosarcoma. When a wide surgical margin can be used and a functional limb can be salvaged, an amputation probably is not required.

Adolescent

The management of primary lymphoma of bone.

From October 1962 through April 1982, 21 patients with the diagnosis of primary lymphoma of bone (18 monostotic, stages IE and IIE; 3 polyostotic) were treated with curative intent. A combination of chemotherapy and radiation therapy was used in 11 patients, local treatment alone in 9 patients, and chemotherapy alone in one patient. Overall 5-year survival for the patients treated with curative intent was 56%. Standard work-up has changed over the 20-year study period. Five-year survival for the subset of eight stage I and II patients with full pretherapy staging was 83%. Prognosis was significantly correlated with extent of pretherapy staging. Treatment parameters that also seemed to predict outcome were the aggressiveness of chemotherapy and the use of irradiation or surgery for local-regional disease; the only local failure occurred in the patient who received chemotherapy alone. Complications of radiation therapy alone and in combination with chemotherapy are discussed and correlated with irradiation dose. Radiation therapy techniques are described, and a management approach is recommended.

Adolescent

Carcinoma of the intact uterine cervix, stage IB-IIA-B, greater than or equal to 6 cm in diameter: irradiation alone vs preoperative irradiation and surgery.

This is an analysis of 123 patients with Stage IB-IIA-B carcinoma of the intact uterine cervix, 6 cm or greater in diameter, who were treated with curative intent at the University of Florida with radiation alone or radiation followed by a hysterectomy between October 1964 and February 1982. There is a minimum follow-up of 2 years in all patients; 87% of all recurrences and 91% of pelvic recurrences occurred within this time period. Examination of pelvic control rates, as well as disease-free survival, showed no significant advantage in pelvic control, disease-free survival, or absolute survival for either treatment group when compared by stage and tumor size. The incidence of severe complications was 6% for patients treated with irradiation alone and 15% for those treated with irradiation and surgery (p = 0.119).

Carcinoma

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Clinical Trials as Topic

Carcinoma of the vagina.

Twenty-two patients with Stage I through IV primary vaginal squamous cell carcinomas treated for cure with radiation therapy are reviewed, with particular emphasis on the relationship of dose to complications and local control. All but 2 patients received 4000 to 6000 rad whole pelvis irradiation plus at least one radium application. Local control was 91%, with an absolute 2-year disease-free survival of 82%. The degree of anaplasia was found to influence prognosis, with all local and distant failures resulting from high-grade lesions. The complication rate was modest, with no fistulae or serious bowel complications. An analysis of total dose (external plus radium) with respect to local failure and complications showed that no major complications occurred at a combined dose below 9000 rad. An analysis of the individual contributions of external irradiation and radium implants showed that all but one very minor complication occurred at a radium dose of 4000 rad or higher. From these data, overall treatment planning and total dose recommendations are made.

Carcinoma, Squamous Cell

Successful strategy for prevention of cytomegalovirus interstitial pneumonia after human leukocyte antigen-identical bone marrow transplantation.

Cytomegalovirus (CMV) interstitial pneumonia is a frequent and often fatal complication of allogeneic bone marrow transplantation. Because therapy for CMV pneumonia was, until recently, largely ineffective, prophylactic methods were explored. This study shows that the strategy of using CMV seronegative blood products for seronegative patients with seronegative donors or weekly administration of intravenous immunoglobulin for all other patients reduced the attack rate of CMV pneumonia. The results of this study are put into the perspective of previously published data.

Adolescent