Robert B. Marcus

Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas.

BACKGROUND An excess risk of second malignancies has been reported in survivors of Ewings sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewings sarcoma and to identify possible causal factors. METHODS Information was derived from a data base that included 266 survivors of Ewings sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received > or = 60 Gy. CONCLUSION The overall risk of second malignancies after Ewings sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.

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.

Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: Surveillance Epidemiology and End Results data.

Purpose The US population-based cancer registry Surveillance, Epidemiology, and End Results (SEER) database provides an opportunity to evaluate the incidence and survival rates of Ewing sarcoma (ES) for the past 3 decades. This analysis reflects trends for the diagnosis of localized versus metastatic disease and changes in ES survival in a setting of wide-ranging cancer care institutions across the United States, which is expected to be different from clinical trials published to date. Materials/Methods Data from the SEER public-access database were reviewed for the diagnosis of ES of the bone among patients of 1 to 19 years of age between 1973 and 2004. Age-adjusted incidence was analyzed for the entire group and for localized and metastatic disease separately over the past 3 decades. Actuarial survival rates were examined for 3 intervals: 1973 to 1982, 1983 to 1992, and 1993 to 2004. Results The overall incidence of ES seemed to remain unchanged with an average of 2.93 cases/1,000,000 reported annually between 1973 and 2004. The proportion of patients with distant metastasis among all ES cases remained in the 26% to 28% range, whereas the percent of localized cases slightly increased from 57% in 1973 to 1982 to 67% in 1993 to 2004 and the proportion of unstaged cases decreased from 17% to 5%. The 5-year survival of localized disease increased from 44% in the first study decade to 68% in the period after 1993, whereas 5-year survival of metastatic disease increased from 16% to 39%. The corresponding 10-year survival increased from 39% to 63% for localized disease and from 16% to 32% for metastatic ES. Conclusions The incidence of ES has not increased appreciably over the last 30 years. A marked decrease in the proportion of unstaged cases may be reflective of diagnostic improvement or changes in reporting. There is a clear improvement in survival for both localized and metastatic disease. Poorer outcome of metastatic patients still warrants intensification of therapy, which is currently being tested in several ongoing trials.

Benign meningiomas: primary treatment selection affects survival.

PURPOSE To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. METHODS AND MATERIALS For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. RESULTS At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical;p = 0.0056), and Karnofsky performance status (> or = 80 vs. < 80; p = 0.0153) as significant variables. CONCLUSION Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important.

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.

Radiotherapy for pituitary adenoma: Long-term outcome and sequelae☆

PURPOSE To review outcome and treatment sequelae in patients treated with external beam radiotherapy for pituitary adenomas. METHODS AND MATERIALS One hundred forty-one patients with pituitary adenomas received radiotherapy at the University of Florida and had 2-year minimum potential follow-up. One hundred twenty-one had newly diagnosed adenomas, and 20 had recurrent tumors. Newly diagnosed tumors were treated with surgery and radiotherapy (n = 98) or radiotherapy alone (n = 23). Patients with recurrent tumors received salvage treatment with surgery and radiotherapy (n = 10) or radiotherapy alone (n = 10). The impact of age, sex, presenting symptoms, tumor extent, surgery type, degree of resection, hormonal activity, primary or salvage therapy, and radiotherapy dose on tumor control was analyzed. Tumor control is defined by the absence of radiographic progression and stable or decreased hormone level (in hormonally active tumors) after treatment. Effect of therapy on vision, hormonal function, neurocognitive function, life satisfaction, and affective symptoms were examined. A Likert categorical scale survey was used for assessment of neurocognitive, life satisfaction, and affective symptom status. Survey results from the radiotherapy patients were compared with a control group treated with transsphenoidal surgery alone. Multivariate analysis used the forward step-wise sequence of chi squares for the log rank test. RESULTS At 10 years, tumor control for the surgery and radiotherapy group (S + RT) was 95% and not statistically different (p = 0.58) than for patients treated with radiotherapy alone (RT) (90%). Patients with prolactin- and ACTH-secreting tumors had significantly worse tumor control, as did patients treated for recurrent tumors. Multivariate analysis for tumor control revealed that only young age was predictive of worse outcome (p = 0.0354). Visual function was either unaffected or improved in most patients, although four patients developed visual loss due to treatment. Hormonal function was affected adversely in 46 of the 93 patients for whom detailed hormonal information was available. Neurocognitive function evaluation revealed that patients in the S + RT group were more likely (p = 0.005) to report difficulty with memory than those in the RT-alone or S-alone groups. No significant difference in life satisfaction or affective symptoms was evident. CONCLUSIONS Pituitary adenomas are well controlled by external beam radiotherapy, either alone or in combination with surgery. Visual symptoms often improve after treatment. Hormonal sequelae require medical intervention in many patients. Neurocognitive sequelae may be different among treatment groups.

Ependymoma: Results, Prognostic Factors and Treatment Recommendations

PURPOSE To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.

Radiotherapy in the management of orbital lymphoma

PURPOSE This retrospective study reviews the treatment technique, disease outcome, and complications of radiotherapy used in the management of lymphoma involving the orbits. PATIENTS & METHODS Thirty-eight patients were treated between May 1969 and January 1995, with a median follow-up of 8.3 years. All patients had biopsy-proven orbital lymphoma. Twenty patients who had limited disease were treated with curative intent, and 18 patients who had known systemic disease were treated with palliative intent. Of the 20 patients treated with curative intent, 14 had low-grade and 6 had intermediate- or high-grade disease. None received chemotherapy. Most patients received treatment with 250 kVP or 60Co radiation, using either an en face anterior field or wedged anterior and lateral fields. Median treatment dose was 25 Gy. Lens shielding was performed if possible. For patients treated for cure, cause-specific survival and freedom from distant relapse were calculated using the Kaplan-Meier method. RESULTS Control of disease in the orbit was achieved in all but 1 patient, who developed an out-of-field recurrence after irradiation of a lacrimal tumor and was salvaged with further radiotherapy. In the patients treated curatively, the 5-year rate of actuarial freedom from distant relapse was 61% for those with low-grade and 33% for those with intermediate/high-grade disease (p = 0.08). Cause-specific survival at 5 years was 89% for patients with low-grade and 33% for those with intermediate/high-grade disease (p = 0.005). Two patients with low-grade disease had contralateral orbital failures; both were salvaged with further irradiation. Acute toxicity was minimal. Cataracts developed in 7 of 21 patients treated without lens shielding and 0 of 17 patients treated with lens shielding. No patient developed significant late lacrimal toxicity. CONCLUSION Radiotherapy is a safe and effective local treatment in the management of orbital lymphoma.

Long-term follow-up of radiotherapy for pituitary adenoma: The absence of late recurrence after ≥ 4500 cGy

Abstract 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 ( 64 months after radiotherapy, with 31 patients (none with bromocriptine) observed 10 to 21 years. We conclude that treatment of pituitary adenoma with ≥ 4500 cGy in 25 fractions can result in a high (≥ 90%) probability of stable long-term control.

Prognostic and treatment factors affecting pelvic control of Stage IB and IIA-B carcinoma of the intact uterine cervix treated with radiation therapy alone.

This is a retrospective analysis of 264 patients with Stage IB and IIA‐B carcinoma of the cervix treated with curative intent at the University of Florida from October 1964 through April 1980. There is a minimum 2‐year follow‐up. Patients dead of distant metastases (13), dead from intercurrent disease (14), or lost to follow‐up (1) less than 24 months from treatment with pelvic disease controlled were excluded from analysis of pelvic control. All patients were included in analysis of complications and survival. Tumor size and hematocrit were noted to be significant prognostic factors with regard to control of disease in the pelvis in Stage IB and IIA cancers. Tumor size and hematocrit also influenced pelvic control in Stage IIB, but to a lesser extent than in Stages IB and IIA. Patient age was a weak prognostic factor for control of disease in the pelvis for Stages IB, IIA, and IIB, but more strongly influenced pelvic control when considered in conjunction with tumor size and hematocrit. Overall treatment time influenced pelvic control in all cases when the size of the lesion was ≧6 cm. in lesions ≧6 cm in diameter, the amount of tumor regression noted at the time of the radium application after 3500 to 4000 rad external beam irradiation was a predictor of pelvic control. Data on treatment complications and survival are included, and future treatment strategies discussed.