Accelerated radiotherapy with concomitant ACNU/Ara-C for the treatment of malignant glioma.

PURPOSE: To evaluate activity and toxicity of simultaneous ACNU and Ara-C with concurrent accelerated hyperfractionated radiotherapy in the treatment of high-grade glioma. PATIENTS AND METHODS: Thirty patients aged 23-71 years (median 47.5), 16 patients with glioblastoma multiforme (GBM) and 14 patients with grade-III glioma, received 93 courses of ACNU/Ara-C (median 4 courses) at following dose levels (ACNU/Ara-C in mg/m2/day): 70/90 (11 courses), 75/100 (36 courses) and 90/120 (46 courses). ACNU was administered IV on day 1 of each cycle, Ara-C as a 2 h-intravenous infusion on days 1-3. Patients received concomitant radiation therapy with 2 daily fractions of 1.75 Gy up to 57 Gy (median). RESULTS: Median survival of all patients was 13 months, 11 months for GBM and > 28 months for grade-III glioma; 31% (9 patients) survived longer than 24 months. The percentage of grade IV hematological toxicity was dose-dependent: 33% at the 70/90 dose level, 40% at 75/100 and 58% at 90/120. Six patients required platelet transfusion, 1 patient red blood cells; no febrile neutropenia occurred. Among 18 patients evaluable for response, 3 (17%) showed PR, 8 (44%) NC and 7 (39%) PD at completion of chemoradiation. No acute or late neurological toxicity occurred in this study. Younger age (p = 0.0001) and grade-III histology (p = 0.0009) were important prognostic factors for prolonged survival. CONCLUSION: This chemoradiation regimen is active in malignant gliomas and can be safely recommended at a dose level using 70 mg/m2 ACNU together with 90 mg/m2 Ara-C.

Supratentorial low-grade glioma: results and prognostic factors following postoperative radiotherapy.

BACKGROUND AND PURPOSE: To assess treatment outcome and prognostic factors following postoperative external radiotherapy in 77 patients with low-grade glioma. PATIENTS AND METHODS: Between 1977 and 1996, 45 patients with astrocytoma, 14 with oligodendroglioma and 18 with mixed glioma received postoperative radiotherapy with a median total dose of 52 Gy (range, 45 to 61 Gy). Sixty-seven patients were treated immediately following surgery, 10 patients with tumor progression. The influence of various factors including histology, gender, age, seizures, duration of symptoms (< or = 6 weeks vs > 6 weeks), CT pattern (enhancement vs no enhancement), type of surgery, total radiotherapy dose and timing of radiotherapy on relapse-free survival and overall survival was investigated. RESULTS: The median overall survival time was 81 months, the 5- and 10-year survival rates were 54% and 31%, respectively. The median time to progression was 56 months, while the 5- and 10-year progression-free survival rates were 45% and 24%. Univariate analyses identified the total radiotherapy dose (p = 0.01), duration of symptoms (p = 0.05), the presence of seizures (p = 0.04), and the CT pattern following intravenous contrast (p = 0.005) as significant prognostic factors for overall survival. Progression-free survival rates were influenced by the total dose (p = 0.04), the duration of symptoms (p = 0.01) and CT pattern (p = 0.006). On multivariate analysis, only the CT pattern (enhancement vs no enhancement) remained as independent prognostic factors for both progression-free survival and overall survival. CONCLUSIONS: A minimum total dose of 52 Gy is recommended for the postoperative radiotherapy in low-grade glioma. Tumors with CT enhancement seem to need further intensification of treatment.

Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity.

BACKGROUND: Management strategies for optic pathway gliomas include observation, surgery, irradiation, chemotherapy and a combination of these modalities. It has been the policy of our University Hospital to consider radiation as the standard treatment for progressive optic pathway gliomas. This report describes the clinical presentation, treatment patterns and outcome with special emphasis on the long term functional status of patients with optico-hypothalamic gliomas (OHG). PATIENTS AND METHODS: Between 1975 and 1997, 25 patients with OHG were treated by radiation therapy (RT) following surgery or biopsy. All patients received a local RT with a 0.5-1 cm margin around the lesions as depicted on CT or MRI scans. Age adjusted radiation doses ranged from 45 to 60 Gy with a single fraction size of 1.6-2 Gy. Endpoints of the study were: radiographic response, survival, progression-free survival and time to endocrinologic toxicity as well as the visual function during follow-up. The median follow-up time was 9 years (range, 1.5-23 years). RESULTS: A partial response was noted in six (24%) of the patients, 13 (52%) patients had a stable tumour throughout the observation period and six (24%) patients had a tumour progression. Overall survival and progression-free survival rates were 94 and 69% at 10 years, respectively. A significant influence on progression-free survival was noted for age at diagnosis (P=0.04) and total dose (P=0.05). Nine out of 13 (69%) patients aged below 10 years compared with 3/12 (25%) patients aged above 10 years experienced hypothalamic-pituitary deficiency (P=0.008) during follow-up. As for visual acuity, nine patients had an improvement, another 13 patients a stable situation and three patients a measurable deterioration. Visual field deficits improved in three, remained unchanged in 16 patients and worsened in only one patient. CONCLUSION: Postoperative RT with a total dose above 45 Gy should be considered as standard treatment in OHG with documented progression. Close radiographic monitoring and lifelong yearly evaluation for the need of possible hormone replacement are strongly recommended.

[Neoadjuvant radiochemotherapy in soft tissue sarcomas. Optimization of local functional tumor control]. / Neoadjuvante Radiochemotherapie von Weichteilsarkomen. Optimierung der lokalen funktionserhaltenden Tumorkontrolle.

BACKGROUND: Adequate local control rates > 90% and acceptable functional results are the paramount goals in the treatment of soft-tissue sarcoma. Purpose of this paper is to evaluate response, long-term control, functional outcome and toxicity following neoadjuvant radiochemotherapy (RCT) in advanced and recurrent soft tissue sarcoma. PATIENTS AND METHODS: Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible entered the study. Sixteen patients had primary and 7 patients recurrent sarcoma. The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-course radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of 1 week after 30 Gy) with concomitant chemotherapy using adriamycin (50 mg/m2/d on days 2 and 30) and ifosfamide (1.5 g/m2/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 months). RESULTS: Twenty-two patients underwent surgery with a curative (R0) resection being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-downstaging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 patient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED- and distant-metastases-free survival rates were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dying of septicemia. The functional results were good to excellent in 18/22 (82%) patients. CONCLUSION: Accelerated split-course radiation with 60 to 64 Gy and concurrent chemotherapy using adriamycin/ifosfamide is a safe and effective treatment for soft tissue sarcoma. This regimen may be considered in all cases with recurrent and advanced disease not amenable to primary curative or limb sparing surgery.

Adjuvant radiotherapy for breast carcinoma in men: a 20-year clinical experience.

Breast cancer in men is a rare malignancy. Current knowledge about its natural history and diagnostic and therapeutic management relies on reviews and few retrospective studies. From 1972 to 1993, 21 men were irradiated for operable primary (n = 17) or recurrent (n = 4) breast cancers at our institution. The mean age at initial diagnosis was 60 years (45-79 years). Tumor distribution by stage was: stage I (two), stage II (seven), stage III (six), stage IV (two), and unknown in four cases. Patients received radiotherapy to the chest-wall and ipsilateral lymph nodes (17) and to the axilla (seven). Additionally hormones (two) and chemotherapy (four) were applied in some cases. Follow-up ranged from 24 to 190 months (median, 53 months). At last follow-up (November 1994), nine patients were alive and eight without disease. The median overall survival of the whole group was 69 months (mean, 106 months). The 3-year (70%), 5-year (59%) and 10-year survival rates (46%) were consistent with literature data. Overall, relapse- and disease-free survival rates were better in patients with stage I/II than in those with stage III/IV disease. Univariate analysis revealed more favorable results for patients with negative axillary nodes, patients younger than 60 years, those with centrally localized tumors, and patients with a diagnostic delay of < 3 months, but the differences were not statistically significant. Six patients relapsed who had not received initial adjuvant radiotherapy to the site of their relapse. At last follow-up, 13 patients had distant metastases, and 12 of them are dead of the metastatic disease, which developed less frequently in stage I/II than in stage III/IV disease. Postoperative adjuvant radiotherapy is an essential part of the overall treatment strategy of advanced node-negative and node-positive cancer of the breast in men.

[Role of percutaneous radiotherapy in male breast carcinoma]. / Die Rolle der perkutanen Radiotherapie beim Mammakarzinom des Mannes.

PURPOSE: Breast cancer in men is a very rare malignancy. Current knowledge about its natural history, diagnostic management and overall prognosis is poor and usually relies on reviews and a few retrospective studies. Herein we report about our past 20-year-clinical experience. PATIENTS AND METHODS: From 1972 to 1993, 21 men with histologically verified tumors were irradiated for operable primary (n = 17) or recurrent (n = 4) breast cancers at our institution. Patients received surgery and post-operative radiotherapy to the chest wall and ipsilateral lymph nodes. Additionally hormones and chemotherapy were applied in only a few cases (n = 5). RESULTS: The follow-up ranged from 18 to 184 months (median 46 months). At last follow-up (11/94), 9 patients were alive and 8 without disease. The median overall survival of all patients was 69 (mean: 106) months and the 5-year survival rate 59%. In univariate analysis, a relapse- and disease-free survival advantage was observed for patients with stage I/II disease, with negative lymph nodes, central tumor location, patients younger than 60 years and short interval (less than 3 months) from first symptoms and diagnostic verification of the malignancy. None of these factors, however, was statistically significant due to the low case number. CONCLUSION: Postoperative adjuvant radiotherapy is an essential part of the treatment strategy of advanced node-negative and node-positive cancer of the breast in men. With respect to locoregional tumor control it is a necessary treatment, while it does not influence the rate of distant metastases. The role of adjuvant hormones and chemotherapy management remains unclear from our scarce patient data.