Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.

PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T­category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (

Generation of a bioartificial fibromuscular tissue with autoregenerative capacities for surgical reconstruction.

INTRODUCTION: Anecdotal clinical reports denote first tissue engineering applications entering medical practice. Currently it is still unknown, if these new types of implants will tolerate the specific needs in cancer patients undergoing postoperative chemo- and radiotherapy. METHODS: We implemented a radiotherapy protocol (cumulative dosis 40 Gy) on generated human bioartificial fibromuscular tissues in vitro. We monitored tissue vitality during radiotherapy and tissue recovery (8 weeks follow up period) applying histological methods. RESULTS: The biopsy procedure and seeding techniques yielded a viable 3 dimensional bioartificial human tissue. Radiation resulted in immediate devitalization without destroying tissue integrity. The bioartificial tissue recovered entirely in vitro within 6 weeks. CONCLUSION: Bioartificial human implants appear applicable for surgical reconstruction in oncologic patients potentially facing postoperative radiotherapy.

[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome]. / Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundhöhlenkarzinome. 3-Jahres-Ergebnisse.

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.

[The value of positron emission tomography (PET) in the treatment of patients with cancer of unknown primary (CUP)]. / Bedeutung der Positronenemissionstomographie (PET) für die Behandlung von Patienten mit unbekanntem Primärtumor (CUP).

BACKGROUND: In patients with cancer of unknown primary median survival for localized disease is 20, for disseminated disease 7 months. After diagnostic procedures including MRI or endoscopy, the primary tumor is detected in less than 25%. In the study presented here the value of PET for detection of the primary tumor and a possible dissemination has been investigated and related to therapeutic regimens. PATIENTS AND METHODS: Between May 1998 and February 2001 a total of 52 patients with CUP syndrome, 18 females and 34 males, have been included. At first diagnosis, stage of disease was localized in 43 patients (35 lymphonodal, eight visceral), and disseminated in nine patients (Table 1). After a median of seven (range three to eleven) diagnostic procedures without detection of the primary tumor (Table 2) PET with fluorine-18-fluorodeoxyglucose was performed. RESULTS: Due to the PET result a primary tumor was suggested in 31/52 patients (60%), and confirmed in 21/52 patients (40%). In 16/43 patients (37%) with initially (before PET) localized disease dissemination was detected by PET only, despite various preceding diagnostic procedures (Figure 1). Overall, in 33/52 patients (63%) the PET result had major impact on selection of an individual treatment (Table 3), in case of initially localized disease in 30/43 patients (70%). CONCLUSION: In patients with CUP the PET result is not only of great value for detection of the primary tumor, but in case of initially localized disease also for diagnosis of a possible dissemination. The PET result often has relevant influence on therapeutic management.

Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management.

BACKGROUND: Two to four percent of cancer patients present with CUP syndrome. Median survival for localised disease is 20 and for disseminated disease, seven months. For localised disease, curative treatment is more likely and individual therapeutic strategies become more important. After conservative diagnostic procedures including MRI, the primary is detected in less than 25%. The diagnostic value of PET and its influence on therapeutic strategies was evaluated. PATIENTS AND METHODS: Forty-two patients with localised CUP were investigated from 5 of 98 to 10 of 2000. The presenting site was lymph node metastasis in 34 and visceral metastasis in 8 patients. After a median of 7 (3-11) diagnostic procedures without detection of the primary, but evidence of localised disease, PET was performed with fluorine-18-fluorodeoxyglucose. RESULTS: In 26 of 42 patients (62%), a primary was suggested by PET and confirmed in 18 (43%). In 5 of 18 patients beyond localised disease, additional dissemination, not detected by previous diagnostic measures, was diagnosed by PET. Overall, dissemination was only detected only by PET in 16 of 42 patients (38%). In29 of 42 patients (69%), the PET result influenced selection of the definitive treatment. CONCLUSION: In CUP patients, PET has a certain impact on detection of the primary as well as of the disseminated disease. and may also have a certain impact on therapeutic management.

Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial.

PURPOSE: To investigate prospectively the prognostic value of the time of developing motor deficits before radiation therapy (RT) for post-treatment functional outcome in metastatic spinal cord compression. METHODS AND MATERIALS: From November 1998 until October 1999, 57 patients were included. Two subgroups were formed according to the time of developing motor deficits before RT: 1-14 days (n = 29) and > 14 days (n = 28). Therapeutic effect on motor function was evaluated by an 8-point scale directly, 6, 12, and 24 weeks after RT. Patients with rapid deterioration of motor function within 48 h before RT (n = 14) were evaluated separately. RESULTS: Directly after RT, 26/28 patients (93%) of the group developing motor deficits > 14 days showed improvement of motor function, in comparison to 3/29 patients (10%) of the group 1-14 days (p < 0.001). Deterioration rates were 0% (> 14 days) and 45% (1-14 days). In patients with rapid deterioration of motor function within 48 h before RT, prognosis was poor (improvement 0%, no change 43%, deterioration 57%). Results were comparable 6, 12, and 24 weeks after RT. CONCLUSION: A slower development of motor deficits before RT predicts a better post-treatment functional outcome. In patients with rapid deterioration of motor function within 48 h before RT, prognosis was extraordinarily poor. These results support the findings of our preceding retrospective analysis.

[Simultaneous radiochemotherapy with taxol/carboplatin in advanced operable head-neck tumors. Preliminary results]. / Simultane Radiochemotherapie mit Taxol/Carboplatin bei fortgeschrittenen operablen Kopf-Hals-Tumoren. Vorläufige Ergebnisse.

BACKGROUND: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent and as well in combination drug regimens. In the present outpatient phase-II trial we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable Stage-III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Twelve patients were enrolled in this ongoing trial with a projected number of 30 patients and received 5 cycles of weekly Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3 to 4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: So far 12 patients were evaluable for toxicity and response. Complete response was noted in 8/12 patients (CR 66%). In 6/10 patients (60%) complete pathologic response was documented in the resection specimens. CONCLUSION: Our preliminary results demonstrated excellent clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as preoperative treatment modality in advanced oral and oropharyngeal cancer.

[Nasal T-cell lymphoma of the lethal midline type. Case report and current aspects in the literature]. / Nasales T-Zell-Lymphom-Typ letales Mittelliniengranulom. Kasuistik und aktuelle Aspekte zur Literatur.

A case of nasal T-cell lymphoma as a cause of lethal midline granuloma in a 41-year-old woman is described. Primary chemotherapy as management failed, and tumor control was achieved thereafter by local radiotherapy to a dose of 52 Gy. Fourteen months after diagnosis the patient died in multiorgan failure with involvement of her skin, lung and liver. Present studies give strong evidence that lethal midline granuloma is very often a type of T-cell lymphoma that might be caused by Epstein-Barr virus. According to the literature our findings support the hypothesis that tumors are best treated by local high-dose irradiation.

Synergistic cytotoxic effects of ether phospholipid analogues and ionizing radiation in human carcinoma cells.

BACKGROUND AND PURPOSE: There is growing evidence in recent years that the antiproliferative effects of ionizing radiation may not be exclusively mediated via DNA damage but also by interactions and alterations of cell membrane associated processes. Here, we tested the hypothesis that membrane active cytotoxic ether lipids and analogues may interact with ionizing radiation, enhancing its antiproliferative effects. MATERIALS AND METHODS: The two epithelial tumor cell lines HTB 43 and KB, and the ether lipid resistant subline KBr were treated by a combination of radiation and ether lipids. Cytotoxic effects were measured by colony forming assays and the effects on membrane phospholipids were determined by quantitative thin-layer chromatography of cell lipid extracts. RESULTS: We present evidence that some ether lipids show supra-additive cytotoxic effects with ionizing radiation. These effects seem to depend on the same structural properties of ether lipids that determine their intrinsic cytostatic and cytotoxic activity. Identical growth inhibitory results were achieved when cells were treated before, or 30 min after irradiation. Analysis of major membrane phospholipids revealed no statistically significant differences of phospholipid distribution pattern in cells exposed to both treatment modalities. CONCLUSION: Our data indicate that changes of overall membrane phospholipid composition do not seem to be the mechanism of synergistic antiproliferative activity of ether lipids and ionizing radiation.

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School]. / Zehn Jahre Transplantation von Knochenmark und hämatopoetischen Stammzellen bei Erwachsenen an der Medizinischen Hochschule Hannover.

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

In vivo effects of interleukin-6 on thrombopoiesis in healthy and irradiated primates.

We have studied the in vivo effects of recombinant human interleukin-6 (rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus monkeys. Of the healthy animals, three received rhIL-6 alone (10 micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination with recombinant cynomolgus granulocyte-macrophage colony-stimulating factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in combination with recombinant human granulocyte-CSF (rhG-CSF; 10 micrograms/kg/d, SC), and one received rhIL-6 in combination with recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d, SC). All animals were treated for at least 2 weeks with rhIL-6 or the above mentioned combinations. rhIL-6 alone significantly increased the peripheral blood platelet counts (2- to 3.5-fold). The platelets reached a plateau between days 10 and 15 of treatment. No synergistic effects on platelet numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF, rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet numbers when administered alone. To test whether rhIL-6 might also protect the animal from thrombocytopenia or shorten the time of thrombocytopenia after irradiation, we treated nine animals with total body irradiation (3.8 Gy). Six of the animals were additional treated with rhIL-6 (4 with 10 micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day 28 post irradiation. In these animals, rhIL-6 at the same dose effective in healthy animals (10 micrograms/kg/d) was not capable of protecting the animals from platelet nadir. However, when pegylated rhIL-6 was used at a dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was 71,000/microL as compared with 39,000/microL in control animals and the time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy and irradiated), rhIL-6 did not increase the number of bone marrow megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes. These data suggest that IL-6 acts as "thrombopoietin"-like activity, but not as "megakaryocyte-CSF"-like activity.

PUVA treatment of vitiligo: a retrospective study of 59 patients.

We have performed a retrospective study of 59 patients with vitiligo who received PUVA therapy from 1972 to 1986. Sixteen patients had generalized vitiligo and 43 vitiligo in four locations (focal vitiligo). In both groups there were repigmentation in 44% of the patients. Half of the repigmented patients had improved more than 50%. None developed hypertrichosis, actinic keratosis, lentigines, or skin cancer within the observation period. Regardless of the results of PUVA therapy half of the patients thought PUVA was an acceptable therapy.

Megestrol acetate in cancer cachexia.

This randomized, controlled trial assessed the activity, tolerance, and degree of weight gain and anorexia of two doses of megestrol acetate in patients with advanced cancer and cachexia. Patients received either 480 mg/d or 960 mg/d megestrol acetate or placebo for 8 weeks. As of June 1990, 55 patients had been randomized; 16 died during the 8-week study, and it was too early to evaluate another 5 patients. The remaining 34 patients were included in analyses. The median initial weight loss ranged from 15% to 22% of usual body weight, which shows the severe degree of malnutrition. Further weight loss was seen in 6 of 8 patients in the placebo group compared with only 5 of 15 and 3 of 11 patients in the low-dose and high-dose megestrol acetate groups, respectively. The median further weight loss was comparable in all groups. Six of 15 and 6 of 11 patients in the low-dose and high-dose groups, respectively, gained weight with a median of 3 kg and 4 kg, respectively. A trend showed beneficial effects of megestrol acetate. Appetite improvement was similar in all groups. Due to the small sample size, however, there were no statistically significant differences among the three groups. Side effects of megestrol acetate were mild. In a subgroup of 15 patients, measurement of body water content indicated a decrease of body fat after 8 weeks in the placebo and low-dose groups. Only the high-dose megestrol acetate group showed an increase in both fat and lean body mass, suggesting a positive effect.

Foot spas as a cause of burns.

Within 2 weeks the authors saw two patients with deep burns of their feet caused by foot spas. Both devices had been used according to the manufacturers' instructions and had been approved by The Danish Electric Material Control. Examination however showed that the bottom plate of these devices reached unacceptably high temperatures that far exceeded the stipulation for approval. As a consequence of this report, the rules for approval of foot spas in Denmark have been changed, as well as a warning to persons at risk that should be included in the directions for use in the future.

Calcipotriol (MC 903), a novel vitamin D3 analogue stimulates terminal differentiation and inhibits proliferation of cultured human keratinocytes.

The hormonally active form of vitamin D3, 1,25-dihydroxy vitamin D3 [1,25-(OH)2-D3; calcitriol], regulates the differentiation and proliferation of epidermal keratinocytes in vitro. MC 903 (calcipotriol) is a novel vitamin D3 analogue which is at least 100 times less potent than 1,25-(OH)-2-D3 in its effects on calcium homeostasis. The present study compared the effects of MC 903 and 1,25-(OH)2-D3 on terminal differentiation and proliferation of cultured normal human keratinocytes. Keratinocytes were grown in McCoy's 5A medium supplemented with penicillin (50 IU/ml), streptomycin (50 micrograms/ml), L-serine (4 X 10(-4) M), and 10% human type AB serum. MC 903, 1,25-(OH)2-D3 or 1 alpha-OH-D3 (10(-12) M--10(-8) M) was added with each feeding when cultures became preconfluent. After incubation for 24 h with D3 vitamins, cultures were extracted for transglutaminase, and the enzyme activity was indexed against DNA content. The activity of transglutaminase, the enzyme responsible for cross-linking the proteins of the cornified envelope, was maximally stimulated by 388% with MC 903 (10(-8) M), by 328% with 1,25-(OH)2-D3 (10(-8) M), and by 27% with 1 alpha-OH-D3 (10(-8) M) compared with vehicle. After incubation for 2 weeks the number of keratinocytes with cornified envelopes had increased by 288% with MC 903 (10(-8) M), by 360% with 1,25-(OH)2-D3 (10(-8) M), and by 149% with 1 alpha-OH-D3 (10(-8) M) compared with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)