Results of breast conserving therapy for early breast cancer and the role of mammographic follow-up.

PURPOSE: The following article is a review of 23 years of breast-conserving therapy in our hospital. This study was performed to assess and improve the follow-up care of women with early breast cancer and to evaluate whether or not biannual mammogram is useful. METHODS AND MATERIALS: Between 1972 and December 1995, 3072 women with pathological size pT1 and pT2 breast cancer were treated with conservative surgery and radiation therapy. Eighty-five patients developed a recurrence in the treated breast as the first site of failure, 12 of which had positive axillary nodes. In the following patient study, those with an noninvasive recurrence were excluded. A retrospective assessment of the entire mammographic course was made, starting with the mammogram at the time of original diagnosis to the mammogram of the recurrence. RESULTS: In our study group the probability for local failure ranged from 1 to 2% per year. At 5 and 10 years the actuarial rates were 5 and 10%. The median time to recurrence was 41 months (range 8-161). Twenty-six (31%) recurrences were detected by mammography alone, 10 (12%) by clinical examination only, and 35 (41%) by both methods. For the patients with an ipsilateral recurrence, the overall actuarial 5- and 10-year survival after treatment was 87 and 70%, respectively. The 5-year actuarial rate of survival from salvage mastectomy was 61%. CONCLUSION: Considering the high percentage of recurrences detectable by mammography and the possibility of detection within a short-term interval, we think biannual mammographic follow-up is appropriate for the first years following breast-conserving therapy.

Post-Operative Radiotherapy of the Rhabdomyosarcoma R1H of the Rat.

Purpose. Post-operative radiotherapy (RT) is routinely applied in the treatment of several human tumours. The aim of the present study was to investigate the value of post-operative RT in a rat model.Methods. Experiments were performed using the rhabdomyosarcoma R1H of the WAG/Rij rat. Animals were randomized to different treatment schedules: surgery, RT or a combination of both. Tumours were excised at different sizes (0.1-4.5 g) aiming for complete macroscopic resection. RT (60 Gy in 30 daily fractions over 6 weeks) was applied either primarily or to the former turnout site from the third post-operative day. Tumour growth delay, time to recurrence and local tumour control were used as endpoints.Results. Pre-operative tumour size determined the time and rate of recurrence. The larger the tumour, the shorter the time to relapse and the higher the recurrence rate. The 50% local control rate (LCR(50)) for surgery was found in tumours with a mass of 0.8 g. For post-operative RT a LCR(50) was achieved for tumours with a mass of 1.1 g. For larger turnouts (> 1.1 g), however, the rate and time course of relapse were similar for both the group receiving RT alone and the group receiving post-operative RT.Discussion. In this model the tumour mass at excision governs the prognosis. Relatively small R1H turnouts may recur despite complete macroscopical resection. With regard to the LCR, the outcome for larger tumours is improved with post-operative RT (60 Gy/6 weeks) than compared with surgery alone. The factor is 1.3. Within a certain range of tumour sizes, combined treatment (surgery + RT) can improve the outcome considerably.

[Lobular cancer transformation of the female breast. Mammography diagnosis and clinical relevance]. / Läppchenkanzerisierung der weiblichen Mamma. Mammographische Diagnostik und klinische Relevanz.

Lobular cancerisation was diagnosed in 101 women between 1976 and 1980. Calcification in the mammograms and follow-up without mastectomy were analysed. Therapy was simple biopsy, because the term lobular cancerisation was not established at that time. Surgery was done at the University Clinic for Women and the Elim Hospital at Hamburg. Retrospective analysis of the specimens was performed at the Department of Gynaecological Histopathology of the Hamburg University Clinic. Mammograms were available in 72 cases, showing calcifications in 40 cases. It was impossible to match the calcifications in the mammograms and the histological slides. Hence, a further 23 cases from 1980 to 1990 were analysed, suffering from lobular cancerisation and ductal carcinoma in situ (DCIS). Comparing 13 mammograms showing calcifications, with large-area scans, only two showed corresponding calcifications. Based on these data a specific diagnosis of lobular cancerisation by mammography is impossible. The follow-up of 88 patients with breast-preserving surgery and lobular cancerisation showed ipsilateral invasive carcinoma in three cases (0.35% in a total of 100 follow-up years), ipsilateral DCIS in five, and contralateral invasive breast cancer in one case. The therapy of lobular cancerisation should depend on the coexisting DCIS. There is no additional risk of local recurrence by lobular cancerisation.

[Breast reduction-plasty using the modified Strömbeck-McKissock technique]. / Die Mammareduktionsplastik in modifizierter Strömbeck-McKissock-Technik.

We reported on the results of 703 breast reduction operations performed by a modified technique after McKissock/Strömbeck. Altogether we operated in the last 10 years 360 patients (15-65 years; mean 32 years) at the Johanniter Hospital in Geesthacht. Only such patients were operated on for whom a medical necessity for reduction of the breast was established, such as orthopaedic problems etc. Complications in healing, especially of the nipple, the supporting parts of the nipple, and parenchyma were examined with these different variables: age of the patients, nicotine consumption, weight of tissue taken out, preoperative distance between nipple and jugulum, body weight of the patient in relation to normal weight, length of operation, loss of blood, and parenchymal histology. Life-endangering complications did not occur in any patient. Infections were seen in 2/360 patients (0.6%). All patients were given a perioperative antibiotic prophylactic, usually with Baypen (mezlocillin). Removable haematoma was seen in only 2/703 (0.3%). 100% necrosis of the nipple was seen in 4/703 reduced breast (0.6%), which agrees with Strömbeck's results (10). Other authors count up to 7.1% complete necrosis of the nipple (2n, 15). Nipple necrosis in part (1/3-2/3) was seen in 14/703 (1.8%) mammaplasty. Statistically highly significant correlations were found in all healing disturbances in relation to the amount of reduced tissue, distance of jugulum to nipple and adipositas. Patients with parenchymal lipomatosis had more complications in relation to other histological types (p < 0.05 and p < 0.01). Especially smoking patients showed a correlation to necrosis of the nipple (p < 0.05%), not to parenchymal necrosis. The duration of operation was not in any way connected with the healing complications. With these results it is easier to obtain the patient's informed consent by means of individual explanations of the operation and its risks.

The value of a postoperative radiation therapy in FIGO stage I and II endometrial cancers.

PURPOSE: The incidence of endometrial cancer has increased considerably within the last decades. Due to early symptoms more than 88% of all patients present initially with FIGO stage I or II disease. PATIENTS AND METHODS: One hundred and forty-four patients out of 192 patients with stage I endometrial cancers received surgical treatment alone. Like the remaining 48 patients 39 out of 65 patients with stage II tumors received adjuvant radiation therapy with 50 Gy to the true pelvis. RESULTS: Independent on the chosen treatment results in stage I were influenced by the depth of myometrial invasion (p = 0.023). With a crude 5-year survival rate of 88% patients with less than 33% reached life expectation of matched healthy women. With deeper infiltration crude survival rates were as low as 77%. In stage II tumors 5-year crude survival was elevated 60 to 80% independent on the depth of myometrial infiltration by adjuvant radiation therapy (p = 0.11). CONCLUSIONS: Despite its potential curability and the general knowledge that the prognosis of endometrial carcinomas is governed by a number of factors there are no generally accepted standard treatment modalities available Thus there is great demand for randomized clinical trials.

Nodal involvement in cancer of the uterine cervix: value of lymphography and MRI.

In this study the preoperative staging of lymph node involvement in cervical cancer was analyzed retrospectively in 155 cases. All results were correlated with lymph node histology. One hundred and three patients underwent preoperative lymphography. Twelve of them were investigated by lymphography and MRI (magnetic resonance imaging). One patient was staged Ia, 10 patients were staged Ib and one patient was staged IIb. All patients underwent surgery; 18.5 lymph nodes were removed on average. Histologically lymph node involvement was found in 3 cases. Lymphography was able to detect lymph node involvement correctly in one case (33% sensitivity). We got two false positive results by lymphography (67% specificity). By MRI all cases were classified as nodal negative. MRI did not have advantage over bipedal lymphography in detecting lymph node involvement in our study, even though the results of lymphography were also poor.

Therapeutic effects of antibodies against adhesion molecules in murine collagen type II-induced arthritis.

Adhesion molecules play important roles in immune reactions and inflammatory processes and may constitute attractive targets for immunomodulatory approaches. In this study, blocking mAbs against a series of adhesion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks at the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained with mAbs against CD44 and alpha 4-integrin, respectively, during an observation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs against other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, collagen type I, proteoglycans and the immunogen, bovine collagen type II was affected by mAb treatment to a different extent. In this case, the anti CD4 mAb was the most effective, followed by the anti alpha 4-antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypersensitivity model analyzed for comparison, mAbs against LFA-1/ICAM-1 and alpha 4-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents.

[Measurement of the distance of the rectal mucosa from a gynecologic afterloading applicator based on the drop in performance of a cobalt-60-source]. / Messung des Abstandes der Rektumschleimhaut von einem gynäkologischen Afterloadingapplikator über den Dosisleistungsabfall einer Kobalt-60-Quelle.

PURPOSE: Assessment of the distance from a gynecological afterloading applicator to the rectum mucosa. METHODS: The appropriate afterloading applicator for HDR-Ir-therapy is used for that purpose. A Co-60-source (370 MBq) with a guiding wire is positioned at the tip of the applicator and then withdrawn in steps of 1 cm. For each of these points the maximum dose at the rectum mucosa is measured with an ionisation chamber. From a reference curve it is then possible to determine the distance from the rectum mucosa to the applicator and to mark it in the calculated isodose plan. The actual daily dose to the rectum mucosa is planned not to exceed 3.0 Gy in the maximum. RESULTS: Up to now the measurements were performed in 91 patients. The minimal distances of the rectum mucosa from the applicator were found to range from 5 to 18 mm with an average value of 14 mm. CONCLUSIONS: The comparison of the measurement with the readings of the rectum probe during each session showed, that the method is suitable to avoid an overdose at the rectum mucosa.

[Determinants of observer variability in early diagnostic mammography--a ROC analysis]. / Determinanten der Beobachter-Variabilität bei der Früherkennungsmammographie--eine ROC-Analyse.

As part of the German mammographic study, the participating doctors were given test films of 30 histologically confirmed cases. Regarding the indications for biopsy there was good sensitivity (the median amongst 25 doctors was 0.87). Specificity (median 0.86) could be improved. Comparison of individual results with the majority showed considerable variability within the group of doctors performing mammography. ROC analysis indicated that there was considerable observer variability which was independent from the specialty or praxis characteristics of the participants. The inclusion of mammography in an early diagnostic programme requires continuing education of the participants in this technique. This should be supported by further methods of quality assurance.

[Therapeutic consequences of early detection of locoregional recurrences in breast cancer]. / Therapeutische Konsequenzen der Früherkennung lokoregionärer Rezidive beim Mammakarzinom.

The value of follow-up investigations depends on the therapeutic consequences of early detection of recurrences and metastatic disease. After breast conservation early detection of recurrent disease by physical and apparative examinations has to be aimed for due to a possible curation by salvage surgery. Also in recurrences of the chest wall a great deal of local controls can be achieved when detected early and at smaller sizes. While axillary recurrences can be controlled by surgery and radiation therapy the prognosis is poor in the case of a supraclavicular and retrosternal lymph node involvement. Diagnostic and therapeutic options will be discussed for these five types of recurrences.

Radiation therapy of para-aortic lymph nodes in cancer of the uterine cervix.

From 1965 to 1986, 173 patients with gynaecological cancer received para-aortic radiation treatment using a biaxial-four-segmental-rotating field technique. Seventy-five patients with cervical cancer and proven lymph node involvement were eligible for analysis. Crude survival and disease-free survival in 37 patients with FIGO III and 15 patients with FIGO IVA, receiving initial para-aortic treatment were compared with the corresponding data from patients in whom para-aortic treatment was secondary applied when para-aortic metastases became clinically symptomatic. Five-year survival rates of 37.5% (FIGO III) and 27.3% (FIGO IVA) were encouraging as none of the patients in the secondary group survived for more than 16 months. The number of complications induced by the described method of survived for more than 16 months. The number of complications induced by the described method of para-aortic irradiation appears to be substantially lower than with other methods using equal doses. Five cases of severe but not life-threatening side-effects were observed among 173 treated patients.

Radiation therapy of para-aortic lymph nodes in gynaecologic cancers: techniques, results and complications.

From 1965 to 1986 the para-aortic lymph nodes of 141 patients with gynaecologic cancers were irradiated directly after initial treatment of the primary site was completed. Another 32 patients only received para-aortic radiation treatment when para-aortic metastases became clinically apparent some time later. Radiation therapy was performed using a biaxial-four-segmental-rotating-field-technique. Crude survival of the group with initial para-aortic radiation treatment is far better than of the second group. Only five cases of severe complications due to para-aortic treatment were reported. In order to analyze the reason for such a low number of complications, CT-treatment planning for a typical patient was performed for different methods as they have been described in the literature, also referring to treatment data such as success, total dose and dose-distribution, thus influencing the complication rate. Obviously, the biaxial-four-segmental-rotating-field-technique is a method allowing to deposit a certain dose into the target volume without considerably damaging tissues in the vicinity.

[Split-course neutron and photon irradiation of experimental tumors: the importance of the sequence and interval lengths]. / Zweizeitige Neutronen- und Photonenbestrahlung experimenteller Tumoren: Bedeutung von Sequenz und Intervallänge.

In a split course mixed beam experiment we have investigated the influence of the interval and beam-quality on tumour growth delay. Fast growing sarcomas (SaF) in grey CBA-mice were irradiated with different sequences of neutrons (N) and photons (X) varying the length of time interval from 0 up to 300 minutes between two doses. The tumours were treated with isoeffective doses of X-rays and/or neutrons (XX, NN, NX, XN). In order to achieve a homogeneous radiosensitive cell population, tumours were reversibly made hypoxic by clamping ten minutes prior and during irradiation. Tumour growth delay is dependent on the sequence and on the interval. As expected the growth delay in tumours treated with neutrons only was less dependent on the interval than after pure photon irradiation. Beyond an interval of 30 minutes in the mixed beam schedules the one giving neutrons first was more effective than the one giving photons first.