[Radiation therapy after mastectomy--interdisciplinary consensus puts and end to a controversy. German Society of Senology]. / Strahlentherapie nach Mastektomie--Interdisziplinärer Konsensus beendet Kontroverse. Deutsche Gesellschaft für Senologie]

BACKGROUND: Recent publications of the Danish Breast Cancer Cooperative Group together with data from the British Columbia Trial have stirred major discussions concerning the role of radiation therapy after mastectomy. Different treatment approaches are to be found even within the same cancer center. The German Society of Senology, a cooperative group of all medical disciplines involved in the treatment of breast cancer, has therefore worked out a consensus statement. MATERIAL AND METHOD: The recently published literature and experts opinions, in particular randomized studies since 1997, meta-analyses from the Early Breast Cancer Trialists' Collaborative Group, epidemiological investigations with regard to the time course of distant metastases in breast cancer as well as the current consensus of the American Society for Therapeutic Radiology and Oncology served as the basis for discussion and consulting. RESULTS OF THE CONSENSUS: (1) An optimally performed mastectomy is a major prerequisite for tumor cure. Radical (R0) resection of the tumor as well as dissection of at least 10 lymph nodes from the axillary level I and II should be accomplished. If axillary lymph nodes are involved, the surgical removal of these lymph nodes is not only of diagnostic, but also of therapeutic value, as it reduces the risk for locoregional relapses. (2) Most probably, locoregional relapses do not only indicate, but are also a source for distant metastases. (3) Radiation therapy of the chest wall and the regional lymph nodes increases the overall survival in risk patients and reduces the risk of locoregional relapses. Moreover, radiation therapy improves the prognosis in case of residual tumor or an incomplete axillary dissection. Unequivocal and reasonable indications for radiation therapy after mastectomy include T3/T4-carcinoma, T2-carcinoma > 3 cm, multicentric tumor growth, lymphangiosis carcinomatosa or vessel involvement, involvement of the pectoralis fascia or a safety margin < 5 mm, R1- or R2 resection and more than 3 axillary lymph node metastases. Further reasonable indications, albeit not yet evaluated in clinical trials, include multifocality, extensive intraductal component, negative hormone receptor status, G3-differentiation grade, diffuse micro-calcifications, 1 to 3 axillary lymph node metastases, multiple, non-complete biopsies and age < 35 years. (4) An endocrine therapy with tamoxifen concurrent to radiation therapy is also reasonable--despite some contradictory in-vitro data--as it enhances the apoptotic cell death. The CMF-regimen is usually performed as sandwich procedure, but can also be applied concurrently to radiation therapy, if indicated. Conversely, an anthracycline-containing chemotherapy should be finished prior to postoperative radiation therapy. CONCLUSIONS: Adjuvant radiation therapy after mastectomy improves the 10-year-survival probability up to 10%, at least for risk patients. The hypotheses of Halsted and Fisher do not exclude each other. There are patients, in which the one, and there are patients, in which the other hypothesis applies.

[Economic limits in oncology]. / Wirtschaftliche Grenzen in der Onkologie.

Economic aspects require consideration even in oncology. However, they have to be seen in context with open questions concerning especially the evaluation of therapeutic effectiveness, of methodology, and particularly of ethics. Medical procedures and achievements should primarily be measured against objective results, against effectiveness and benefits. Consequently, the suitability of diagnostic and therapeutic strategies has to be evaluated. Overall objective of medical achievements should be their optimalization, not their maximization. For a physician being aware of his responsibility, the optimal care for his patients always has highest priority. Medical guidelines for diagnosis, treatment and follow-up are the basis for effective and economic patient care. They have to undergo economic evaluation and permanent updating. For systematic collection, documentation and evaluation, the clinical register is the appropriate instrument. For the assessment of medical care, a continuous monitoring of its processes has to be established. The documentation of medical care processes should lead to sustainable cost reductions together with an optimalization of the quality of care.

Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia.

Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1(+)-ALL.

[Breast-conserving therapy in breast carcinoma--the indications and sequelae. The results of a multidisciplinary consensus meeting]. / Brusterhaltende Therapie beim Mammakarzinom--Indikation und Konsequenzen. Ergebnisse einer multidisziplinären Konsensus-Tagung.

A multidisciplinary consensus development conference on the management of breast-preserving treatment in early breast cancer was organized in November 1989 in Berlin. Following a two-day discussion of data presented, conclusions and recommendations were achieved on the indication and limitation of breast conservation, the optimal technique as well as the diagnostic requirements and therapeutic strategies in context with breast conservation including follow-up.

[Therapy of hairy cell leukemia with interferon]. / Therapie der Haarzell-Leukämie mit Interferon.

Hairy cell leukemia is a rare lymphoproliferative disorder which is morphologically characterized by circulating lymphatic cells with prominent 'hairy' cytoplasmatic projections. Patients typically present with pancytopenia and splenomegaly. The bone marrow cannot be aspirated because of reticulin fibrosis. Chemotherapy was unable to influence the course of the disease satisfactorily. Therefore, splenectomy was the treatment of choice. The introduction of alpha-interferons into the therapy of hairy cell leukemia was a decisive breakthrough and is exemplary for the use of interferons in the treatment of malignant diseases. However, there are still many questions to be answered. The discussion of clinical implications is achieving growing importance in consequence of the availability of diverse commercial alpha-interferons for treatment of hairy cell leukemia.

[Therapy of chronic myeloid leukemia with interferon]. / Therapie der chronischen myeloischen Leukämie mit Interferon.

Several modalities are used for treatment of the chronic phase of chronic myelogenous leukemia. Most patients are treated with single agent chemotherapy. However, patients are cured only by isogenic or allogeneic bone marrow transplantation; otherwise the disease regularly proceeds to fatal blastic crisis. Alpha-interferon has an antiproliferative activity against hematopoietic cells in vitro and in vivo. We have treated 10 patients with the chronic phase of Philadelphia--chromosome-positive chronic myelogenous leukemia with alpha-interferon. The median duration of the disease was 10 months. Five patients were previously untreated and five achieved hematologic remission. Patients with a disease duration of less than 1 year, who had had no or only minimal pretreatment, showed the best response rates. These experiences confirm published data on interferon therapy. It remains to be determined whether interferon treatment and the hereby induced suppression of the Philadelphia-chromosome-positive cell clone in some patients will improve survival.

Chemoprophylaxis of bacterial infections in granulocytopenic patients with ciprofloxacin.

The trial was conducted to evaluate the antimicrobial prophylactic efficacy of ciprofloxacin in reducing the frequency of infections in granulocytopenic patients. The frequency of infections was evaluated in 34 patients with acute non-lymphoblastic leukemia, acute lymphoblastic leukemia, blast crisis of chronic myelogenous leukemia and other malignancies. 46 courses of oral prophylactic treatment with 500 mg ciprofloxacin twice daily were administered. While there was no infection in 61% of treatment courses, fever over 38 degrees C (axillary) occurred in 39%. 6 patients had a fungal pulmonary infection, one patient a supposed viral pneumonia, and only two patients had a documented bacterial infection. There were no severe side effects. We conclude that ciprofloxacin is a potent drug in prophylaxis of bacterial infections in cancer patients with therapy-induced granulocytopenia.

Idarubicin in refractory acute leukemia.

10 patients with resistant or relapsed acute leukemia (9 AML, 1 ALL) were treated with idarubicin (4-demethoxydaunorubicin) in combination with cytosine arabinoside +/- etoposide. All patients had been heavily pretreated. 9 AML-patients had previously received 2-4 cycles of TAD-9 regimen. 2 complete and 1 partial remission were achieved. 1 patient died from septicemia in bone marrow aplasia without leukemic cells. 6 patients did not respond to idarubicin-based salvage treatment. The median survival from start of therapy was 4 months. Idarubicin-based combination chemotherapy is effective in relapsed acute leukemia, even in patients intensively pretreated with anthracyclines.

Empiric antibiotic treatment of infections in myelosuppressed cancer patients. Preliminary results.

A prospective, randomized study was performed to compare the efficacy and safety of mezlocillin plus sisomicin (Regimen A) and cefamandole plus tobramycin (Regimen B). Sixty-one episodes of documented infections were treated in 49 adult myelosuppressed cancer patients. About two-thirds of the patients treated with either regimen responded to this antibacterial therapy. The patients failing to respond to the initial therapy were treated with additional antibiotics, either with the empiric Regimen C (cefotaxime plus amikacin plus azlocillin) or with antibiotics selected on the basis of bacteriological results (Regimen D). With these schedules, the over-all response rate was increased to about 90%. The data suggest that febrile granulocytopenic cancer patients may profit from this empiric and sequential antibiotic treatment.

Correlation of chromosomal aberrations in a myeloma cell line with tumorigenicity in nude mice.

A human myeloma cell line (L 363) exhibiting several markers of malignancy including a 14q + chromosome marker was not tumorigenic in nude mice. Long-term cultivation in vitro resulted in new subclones with slight, well-defined chromosomal differences to the original line. Certain subclones turned out to have a growth advantage in vitro and became tumorigenic after transplantation in nude mice. A strong correlation between changes in the chromosome I constellation resulting in the threefold dose of long arm-material and the increased proliferative potential in both experimental systems was found.

[Chronic lymphoproliferative disorder resembling hairy-cell leukemia (author's transl)]. / Chronische lymphoproliferative Erkrankung unter dem Bild einer Haarzell-Leukämie.

Seven patients are presented with a chronic lymphoproliferative disorder characterized clinically by splenomegaly, no or discrete lymphnode enlargement, and a varying degree of cytopenia. In blood and bone-marrow smears lymphoid cells of "hairy" appearance are demonstrable which may contain tartrate-resistant acid phosphatase. The finding of a nodular bone-marrow infiltration without fibrosis as well as that of a nodular infiltration of the spleen originating in the white pulp are incompatible with the diagnosis hairy-cell leukemia and place the disease near to chronic lymphocytic leukemia (CLL) or leukemic immunocytoma respectively. A detailed cytologic and cytochemical examination of the infiltrating cells shows deviations from the typical enzymatic pattern of hairy cells and from known enzymatic constellations in CLL and related lymphoproliferative disorders. Thus, we are dealing with an intermediate form, difficult to classify, the separation of which nevertheless seems to be important for therapeutical reasons.