[Local control and distant metastasis after cystectomy in bladder carcinoma].
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Biomedical subjects
Publications and source records attributed to J Dunst.
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Therapy of Ewing's sarcoma consists of adequate local treatment for control of the primary tumor (surgery or radiotherapy or a combination of both) and systemic therapy. Tumors with favorable prognosis (small tumor volume, good response to chemotherapy) may be managed by a single local modality. In tumors with poor prognosis, combined local treatment (surgery plus radiotherapy) seems to improve local control and survival. As an innovative approach, preoperative radiotherapy for high-risk tumors is investigated in the EICESS-92-study.
PURPOSE: We present an update analysis of the multiinstitutional Ewing's sarcoma study CESS 86. METHODS AND MATERIALS: From January 1986 through June 1991, 177 patients with localized Ewing's sarcoma of bone, aged 25 years or less, were recruited. Chemotherapy consisted of four 9-week courses of vincristine, actinomycin D, cyclophosphamide, and adriamycin (VACA) in low-risk (extremity tumors < 100 cm3), or vincristine, actinomycin D, ifosfamide, and adriamycin (VAIA) in high-risk tumors (central tumors and extremity tumors > or = 100 cm3). Local therapy was an individual decision in each patient and was either radical surgery (amputation, wide resection) or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy (45 Gy plus boost). Irradiated patients were randomized concerning the type of fractionation in either conventional fractionation (once daily 1.8-2.0 Gy, break of chemotherapy) or hyperfractionated split-course irradiation simultaneously with the VACA/VAIA chemotherapy (twice daily 1.6 Gy, break of 12 days after 22.4 Gy and 44.8 Gy, total dose and treatment time as for conventional fractionation). For quality assurance in radiotherapy, a central treatment planning program was part of the protocol. RESULTS: Forty-four patients (25%) received definitive radiotherapy; 39 (22%) had surgery, and 93 (53%) had resection plus postoperative irradiation. The overall 5-year survival was 69%. Thirty-one percent of the patients relapsed, 30% after radiotherapy, 26% after radical surgery, and 34% after combined local treatment. The better local control after radical surgery (100%) and resection plus radiotherapy (95%) as compared to definitive radiotherapy (86%) was not associated with an improvement in relapse-free or overall survival because of a higher frequency of distant metastases after surgery (26% vs. 29% vs. 16%). In irradiated patients, hyperfractionated split-course irradiation and conventional fractionation yielded the same results (5-year overall survival of definitively irradiated patients 63% after conventional fractionation and 65% after hyperfractionation; relapse-free survival 53% vs. 58%; local control 76% vs. 86%, not significant). The six local failures after radiotherapy did not correlate with tumor size or response to chemotherapy. Radiation treatment quality (target volume, technique, dosage) was evaluated retrospectively and was scored as unacceptable in only 1 out of 44 patients (2%) with definitive radiotherapy. Grade 3-4 complications developed in 4 out of 44 (9%) patients after definitive radiotherapy. CONCLUSIONS: Under the given selection criteria for local therapy, radiation therapy yielded relapse-free and overall survival figures comparable to radical surgery. Hyperfractionated split-course irradiation simultaneously with multidrug chemotherapy did not significantly improve local control or survival.
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PURPOSE: In a pilot-study patients with primarily non-resectable rectal cancer received a pre-operative radiochemotherapy to assess the tolerance and efficacy of this treatment protocol. PATIENTS AND METHOD: Twenty patients with non-resectable rectal cancer (Mason CS III-IV) have been irradiated from September 1989 through February 1994. The total dose, calculated at the isocenter, was 50.4 Gy with 5 fractions of 1.8 Gy per week with a small volume boost in selected cases. Chemotherapy was administered on 5 consecutive days in week 1 and 5 with 1000 mg/m2 5-FU per day as continuous infusion over 120 hours. RESULTS: The treatment was well tolerated. Acute toxicity included 1 grade III-dermatitis, 7 grade II-enteritis, 1 grade III- and 3 grade II-leucopenia. Seventeen out of 20 patients were resected 6 weeks after radiochemotherapy, 3 patients had no surgery (1 toxic death due to septicemia, 1 refusal of surgery after complete remission, 1 thrombocytopenia due to liver cirrhosis), all 3 had at least partial remission of their tumors. Fourteen out of 17 (82%) resections were curative (R0) with 1 additional R1- and 2 R2-resections. Ten out of 14 (71%) curative resected patients had no lymph node metastasis. A detailed histological examination showed regression in 15/16 tumors with fibrosis and vascular wall changes. Nine out of 16 patients had only minimal residual tumor. CONCLUSIONS: In this pilot study, pre-operative radiochemotherapy was well tolerated. The relatively high rate of curative resections and marked histological tumor regressions of this approach requires further investigations in a randomized trial.
BACKGROUND: We have examined the in-vitro radiosensitivity of lymphocytes in patients with extreme acute and chronic reactions after curative radiotherapy under the assumption of increased genetic radiosensitivity. PATIENTS AND METHODS: 16 patients (14 females, 2 males, age 40 to 69 years) were retrospectively examined 1 to 108 months after radiotherapy. All had undergone definitive or postoperative curative radiotherapy for cancer (12 breast cancer, 2 lung, 1 bladder, and 1 head and neck cancer). None of them had known genetic disorders with increased radiosensitivity. Four patients were considered as having probably increased radiosensitivity; they had shown poor tolerance to radiotherapy (1 severe acute reaction with cessation of radiotherapy in bladder cancer and subsequent bladder shrinkage after 45 Gy, 1 acute skin reaction well above average with subsequent fibrosis after irradiation for regional recurrence of breast cancer, 1 radiation myelitis after palliative irradiation with 5 x 5 Gy for lung cancer, 1 severe acute reaction after mediastinal irradiation for lung cancer). Twelve patients were considered as having normal tolerance to radiotherapy. They had tolerated radiotherapy well with normal acute reactions and no or minimal signs of late radiation sequelae. Lymphocyte cultures were prepared from all patients and irradiated with 0.7 and 2 Gy, respectively; 1 culture served as control (0 Gy). Chromosomes 1, 2, and 4 were stained using fluorescence in-situ hybridization (FISH) with a 3-colour-chromosome-in-situ suppression technique. Chromosomal breaks were counted in 200 to 1000 mitoses. Radiation sensitivity was expressed as radiation-induced breaks per mitoses corrected for breaks at 0 Gy. The probes were coded and the examiner did not know the clinical course. RESULTS: Significant differences in interindividual radiation sensitivity were detectable. The frequency of radiation-induced breaks/1000 mitoses ranged from 70 to 556 after 0.7 Gy and from 420 to 1210 after 2 Gy. The 4 patients with increased clinical radiation sensitivity showed also increased chromosomal radiation-induced damage as compared to the 12 patients with normal radiation tolerance (469 +/- 103 vs. 126 +/- 79 breaks/1000 mitoses induced by 0.7 Gy, p = 0.0011, and 864 +/- 258 vs. 574 +/- 119 breaks/1000 mitoses induced by 2 Gy, p = 0.019). CONCLUSIONS: Patients with increased clinical radiosensitivity exhibited increased chromosomal damage in lymphocytes in vitro measured with chromosome painting with a FISH-technique. This technique may be useful to detect patients with severely enhanced radiosensitivity. The results suggest that if radiosensitivity is abnormally elevated this may be present and detectable in different organs.
PURPOSE: Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS: From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS: The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS: Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.
BACKGROUND: Chemotherapy is currently investigated in young children with medulloblastoma with the objective to omit or even delay craniospinal irradiation. CASE REPORT: We report a case of very early meningeal progression of medulloblastoma during postoperative chemotherapy in a 2.5-year-old boy. At 2 3/12 years of age, the boy developed ataxia. One month later, a malignant cerebellar tumor was diagnosed by magnetic resonance tomography. The boy underwent a macroscopically complete resection. Histological diagnosis revealed medulloblastoma. Postoperative magnetic resonance scans showed no residual disease or spinal seedings and the patient was classified as T3 M0 according to Chang. Three weeks after surgery, chemotherapy with ifosfamide, VP 16, and methotrexate was started. One month later, a positive Babinski sign developed, computed tomography scans showed no abnormalities. Chemotherapy was continued with cisplatin plus cytosine arabinoside as well as cisplatin plus ifosfamide and methotrexate. After 4 months of chemotherapy, a seizure and weakness of the legs occurred. Magnetic resonance scans revealed massive meningeal seeding and 400 tumor cells/microliters were found in the cerebrospinal fluid. Craniospinal irradiation was initiated, and the neurologic symptoms resolved. The boy died, however, 4 months later due to progressive spinal disease. CONCLUSIONS: The early and rapid meningeal progression during chemotherapy is uncommon. The case demonstrates the difficulties of diagnosis and differential diagnosis.
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BACKGROUND: Adjuvant therapy of rectal cancer has been investigated in randomized trials during the past 20 years. The actual data allow to draw some principle conclusions. RESULTS: Adequate surgical treatment is the basis for any adjuvant therapy. However, even in case of optimal surgery local recurrence rates of 20 to 30% are to be expected for stage II/III patients with 5-year survival figures in the range of 40 to 60%. In some series, e.g. the results of the Surgical Department of the University of Erlangen, a significant correlation between local control and survival exists. Postoperative radiotherapy decreases the risk of local recurrence but has--as postoperative chemotherapy--only marginal impact on survival. Combined adjuvant treatment (radiotherapy plus 5-FU-chemotherapy) has significantly increased the 5-year survival figures by 10 to 15% in 2 randomized trials and is considered as standard adjuvant treatment. From a radio-oncological point of view, most studies may be criticized at least in part because of low pre-operative doses, inadequate technique without individual treatment planning and shielding, unfavourable fractionation, or dose reductions of radiotherapy in case of chemotherapy. Further improvement of local efficacy of radiotherapy and reduction of therapy-related toxicity seems therefore possible. Innovative approaches in radiation oncology mainly include pre-operative strategies. CONCLUSIONS: Postoperative radiochemotherapy (locoregional irradiation with 50 Gy, small volume boost, 6 courses with 5-FU) is recommended as standard adjuvant treatment outside clinical trials for stage II/III patients after curative surgery. Prospective studies should mainly focus on neoadjuvant treatment concepts.
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