BACKGROUND AND PURPOSE: Lymphocytes of a small fraction of cancer patients responded to in vitro irradiation with an extreme chromosomal reaction. A large portion of the observed chromosome aberrations were complex chromosomal rearrangements (CCR). The present study is an attempt to define the impact of CCR on the predictive detection of an intrinsic clinical radiosensitivity in cancer patients in more detail. MATERIALS AND METHODS: A three-colour 'FISH-painting' technique (chromosome in situ suppression (CISS) hybridization) was used for the detection of chromosomal rearrangements, induced by in vitro irradiation, in 81 samples of peripheral blood lymphocytes from 66 cancer patients. Thirty-three of those were assigned for radiation therapy, the others having just undergone radiation therapy. Seven healthy individuals served as controls. RESULTS: CCRs are a very rare event in non-irradiated cells. Lymphocytes of patients who had just undergone therapeutic irradiation, however, not only exhibited high basic frequencies of CCR but also responded to in vitro irradiation with a more drastic increase of CCR than did the lymphocytes of non-exposed patients. A high inter-individual variability of the reaction to in vitro irradiation could be generally stated. The lymphocytes of patients with clinical signs of an outstanding radiosensitivity responded with an unusually high frequency of CCR. The total number of CCRs detected by CISS was found to be dependent on the interval from a previous radiation therapy and was slightly influenced by previous cytostatic therapy. Irrespective of these influences, patients with clinically defined radiation hypersensitivity were those with the highest radiosensitivity also in cytogenetic terms (including CCR). CONCLUSION: The successful use of FISH-painting for the detection of CCR, in addition to the general breakage frequency, highlights its suitability in the identification of individual hypersensitivity to ionizing radiation. The time-consuming cytogenetic examination can be considerably reduced by its use.

Chromosome Aberrations↗

PubMed1997

Ewing's sarcoma of the femur. Prognosis in 69 patients treated by the CESS group.

We reviewed the treatment outcome of 69 patients with Ewing's sarcoma of the femur. The patients received chemotherapy according to the CESS 81 (n 14), CESS 86 (n 43), and CESS 91P (n 12) protocols. The 10-year relapse-free survival rates were 36%, 65%, and 65% (p = 0.01). 68 patients received local treatment. The primary tumor was treated by surgery without radiotherapy in 28 patients; 1 developed a local recurrence and 7 metastases. 10 patients received radiotherapy alone; 4 developed metastases and 4 local recurrences and metastases. 30 cases had a combination of surgery and radiotherapy; 7 developed metastases and 1 a local recurrence and metastasis. The survival of patients after radiotherapy alone was worse than that of patients after surgery with/without radiotherapy (p = 0.005). Pathological fractures (n 16) did not influence the prognosis.

Adolescent↗

PubMed1996

Significance of surgical margin on the prognosis of patients with Ewing's sarcoma. A report from the Cooperative Ewing's Sarcoma Study.

BACKGROUND: There is little information regarding an adequate surgical margin for local control of Ewing's sarcoma. METHODS: Two hundred and forty-four patients (PTS) with Ewing's sarcoma who were registered in the Cooperative Ewing's Sarcoma Studies underwent surgical treatment. Ninety-four PTS underwent definitive surgery (surgery alone), 131 PTS received postoperative irradiation, and 19 PTS received preoperative irradiation. The surgical margins were distributed as follows: radical, 29 PTS; wide, 148 PTS; marginal, 39 PTS; and intralesional, 28 PTS. The impact of the surgical margin on the treatment outcome of PTS was analyzed statistically. RESULTS: The local or combined (local recurrence and systemic metastasis) relapse rate after surgery with or without irradiation was significantly lower compared with that after definitive irradiation (irradiation alone) (7% vs. 31%, P < 0.0001). The local or combined relapse rate after complete resection (radical or wide margin) with or without irradiation was less compared with that after incomplete resection (marginal or intralesional margin) with or without irradiation (5% vs. 12% P = 0.0455). The local or combined relapse rate did not greatly decreased after irradiation after incomplete surgery (from 14% to 12%). In both groups of good (viable tumor cells < 10%) and poor (viable cells > or = 10%) histologic response, the difference in systemic or combined relapse rate between patients undergoing complete and incomplete surgery was not significant. The 10-year overall survival of the PTS for each of the margins was distributed as follows: radical, 58%; wide, 65%; marginal, 61%; and intralesional, 71% (P = not significant). CONCLUSIONS: Surgery in patients with Ewing's sarcoma adds to the safety of local control. Under the current treatment regimen with intensive chemotherapy and irradiation, complete resection of the tumor appears capable of decreasing the risk of local recurrence.

Adolescent↗

PubMed1996

Use of a three-color chromosome in situ suppression technique for the detection of past radiation exposure.

A three-color chromosome in situ suppression technique and classical cytogenetic analysis were compared for the detection of chromosomal aberrations in blood lymphocytes of 27 patients who had undergone radiation therapies from 1 month to 9 years ago. Depending on the respective regimens of therapy, a high variability was found in the aberration data. Aberration rates depended on the interval between exposure and scoring rather than on the locally applied radiation doses, which were rather uniform among most patients. Chromosome in situ suppression was found to be superior to classical cytogenetics with respect not only to the spectrum of detectable aberrations but also to the uncovering of long-term effects of irradiation. Of particular interest were the relative stability of the frequency of radiation-induced reciprocal translocations and the utility of chromosome in situ suppression to uncover complex rearrangements.

Chromosome Aberrations↗

PubMed1996

[The late cardiac sequelae after mantle-field irradiation. The results in Erlangen's patient caseload].

PURPOSE: We have retrospectively evaluated the cardiac function in patients after mantle-irradiation for Hodgkin's disease. PATIENTS AND METHODS: Forty-three patients, mean age 39.8 +/- 13 years, who had been treated with mantle-irradiation from 1979 through 1984 at the University of Erlangen-Nürnberg, were examined. All of them were in first remission at 5 to 11 years (mean 8.1 years) after radiotherapy (n = 24) or combined modality treatment (n = 19). Mantle-irradiation had been administered through equally weighted anterioposterior-posterioanterior portals with 5 fractions of 2 Gy per week up to a total mediastinal dose of 41.8 +/- 7 Gy (including boost). The examination program included anamnesis, physical examination, Doppler echocardiography and ergometry. Hundred and twenty-two non-irradiated volunteers and cardiological patients were used as control group. RESULTS: None of the patients suffered from clinical symptoms. Pericardial thickening was present in 26%. The left ventricular end-systolic diameter (31.3 +/- 5.5 mm, normal value 26 to 42 mm) and the thickness of the left ventricular posterior wall (8.1 +/- 1.8 mm, normal value 6 to 11 mm) were within the normal range. The left ventricular ejection fraction was also normal (67.1 +/- 8% in patients versus 67.0 +/- 8% in control subjects). Evaluation of diastolic parameters, however, revealed significant changes. The isovolumic relaxation time was significantly decreased as compared to the control group (38.8 +/- 17 ms versus 50.8 +/- 21 ms, p < 0.05). The same we found for the shortening fraction (33.6 +/- 6% versus 38.1 +/- 6%, p < 0.05). The most significant changes were found after combined modality therapy, especially after radiotherapy and anthracycline-based chemotherapy. 30% of the patients were tachycardic (pulse > 100/min) at rest. At ergometry, the frequency of signs of ischemia (5%), conduction disturbances (2%), and rhythm disturbances (7%) was not elevated. CONCLUSIONS: In this retrospective investigation, patients after mantle irradiation with modern techniques showed only minimal cardiologic abnormalities within the first 10 years after treatment. The most sensitive parameters were the isovolumic relaxation times. The clinical relevance of such findings remains to be defined. Pathophysiologically, our findings (decreased relaxation time plus tachycardia) support the theory that myocardial damage after radiotherapy may result in subsequent increased beta-receptor density as proposed by Schultz-Hector et al. [21] on the basis of experimental data.

Adult↗

PubMed1996

[The prognostic significance of intramammary recurrence in breast-conserving therapy].

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Breast Neoplasms↗

PubMed1996

[Surgery versus radiotherapy in Ewing's sarcoma with good prognosis. Analysis of the CESS-86 data].

PURPOSE: The evaluation of radiotherapy and surgery as exclusive local treatment in comparably selected subgroups of patients with Ewing's sarcoma on the basis of the CESS 86-data. PATIENTS AND METHODS: In the German multicenter Ewing's sarcoma study CESS 86, treatment consisted of four 9-week-courses of VACA- or VAIA-chemotherapy plus local therapy. VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin) was given in low-risk extremity tumors with a tumor volume below 100 cm3. High-risk patients with central lesions or a tumor volume > 100 cm3 received VAIA (ifosfamide instead of cyclophosphamide). Local therapy started after one complete chemotherapy course in week 10. Based on an individual decision in each patient, local therapy was either radical surgery or resection plus postoperative irradiation with 45 Gy or definitive radiotherapy with 60 Gy. Because of poor results with radiotherapy in a preceding study, it was intended to restrict irradiation to patients with small lesions. RESULTS: Hundred and seventy-seven protocol patients were recruited from January 1986 through June 1991 and 176 received local therapy: 39 underwent radical surgery, 44 received definitive radiotherapy and 93 were treated with resection and postoperative irradiation. The median tumor volume was higher in patients with radiotherapy as compared to combined local treatment or radical surgery, 156 cm3 versus 140 cm3 versus 102 cm3. The overall 5-year survival after radiotherapy and surgery was nearly identical, 63% versus 67% for the whole group 75% versus 65% in tumors < 100 cm3 volume and 65% versus 67% in tumors with 100 cm3 to 600 cm3 volume, respectively. CONCLUSIONS: With regard to tumor volume, the most important single prognostic factor in Ewing's sarcoma, irradiated patients were poorer selected than surgically treated patients despite the fact that a selection of good-risk patients for radiotherapy was intended. The nearly identical survival figures after surgery and radiotherapy suggest that radiotherapy is as effective as surgery if selection of patients is comparable.

Adult↗

PubMed1996