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Biomedical subjects

M Stuschke

Publications and source records attributed to M Stuschke.

At least 19 recordsLinked to original sources
PubMed2006

Induction chemotherapy, concurrent chemoradiation and surgery for Pancoast tumour.

The traditional treatment of Pancoast tumour with local approaches (surgery, radiotherapy or a combination of both) leads to a poor outcome due to the high rate of incomplete resection and the lack of systemic control. The aim of the present prospective feasibility study was to determine whether a trimodality approach improves local control and survival. Patients with stage IIB-IIIB Pancoast tumour received induction chemotherapy (three courses of split-dose cisplatin and etoposide or paclitaxel) followed by concurrent chemoradiotherapy (a course of cisplatin/etoposide combined with 45 Gy hyperfractionated accelerated radiotherapy). After restaging, eligible patients underwent surgery 4-6 weeks post-radiation. A total of 31 consecutive patients with T3 (81%) or T4 (19%) Pancoast tumour were enrolled in the study. Induction chemoradiotherapy was completed in all patients without treatment-related deaths. Grade 3-4 toxicity was observed in 32% of cases. In total, 29 (94%) patients were eligible for surgery. Complete resection was achieved in 94% of patients. The post-operative mortality rate was 6.4% and major complications arose in 20.6% of the patients. The median survival was 54 months with 2- and 5-yr survival rates of 74 and 46%, respectively. In conclusion, this intensive multimodality treatment of Pancoast tumour is feasible and improves local resectability rates and long-term survival as compared with historical series.

Adult↗
PubMed2006

[High-dose rate brachytherapy for high-risk prostate cancer].

To estimate disease-free survival it is necessary to allocate patients into tumor risk groups: locally advanced prostate carcinoma with extracapsular spread or localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason 7. Particularly for patients with intermediate and high-risk disease early PSA relapse is of major interest. This phenomenon could be a consequence of current inadequate imaging of lymph node or bone metastasis or as a consequence subclinical metastatic spread remains undetectable during radical treatment. However, tumor biology itself could lead to the progression of the disease in the high-risk group. As a consequence, risk-adapted therapy is very important in these cases. The applied radiation dose plays an important role in radiotherapy. Several publications have shown that the biochemical relapse correlates with the generally accepted risk factors and the radiation dose. Regarding this, high-quality treatment planning and HDR brachytherapy combined with EBRT (external beam radiation therapy) leads to good treatment results in selected groups. So far in our own experience, HDR brachytherapy in combination with EBRT is a successful form of treatment with few acute and late side effects in the first 42 patients examined. First results concerning to PSA relapse-free time, quality of life, miction, and erectile function are promising.

Biomarkers, Tumor↗
PubMed2005

Targeting of Rad51-dependent homologous recombination: implications for the radiation sensitivity of human lung cancer cell lines.

The aim of the present work was to study the role of Rad51-dependent homologous recombination in the radiation response of non-small-cell lung cancer (NSCLC) cell lines. A dose- and time-dependent increase in the formation of Rad51 and gamma-H2AX foci with a maximum at about 4 and 1 h after irradiation, followed by a decrease, has been found. The relative fraction of cells with persisting Rad51 foci was 20-30% in radioresistant and 60-80% in radiosensitive cell lines. In comparison, a higher fraction of residual Dsb was evident in cell lines with nonfunctional p53. Transfection with As-Rad51 significantly downregulates radiation-induced formation of Rad51 foci and increases apoptosis, but did not influence the rejoining of DNA double-strand breaks. Interestingly, wortmannin, a well-known inhibitor of nonhomologous end-joining, also inhibits Rad51 foci formation. In general, there was no correlation between the clonogenic survival at 2 Gy and the percentage of initial Rad51 or gamma-H2AX foci after ionising radiation (IR). The most reliable predictive factor for radiosensitivity of NSCLC cell lines was the relative fraction of Rad51 foci remaining at 24 h after IR. Although most of the Rad51 foci are co-localised with gamma-H2AX foci, no correlation of the relative fraction of persisting gamma-H2AX foci and SF2 is evident.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

High-dose chemotherapy with autologous stem cell transplantation in patients with oligometastatic breast cancer.

The purpose of this prospective trial was to study a combined-modality treatment including local consolidation by surgery or radiotherapy and high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell (PBSC) transplantation. In all, 48 patients with oligometastatic breast cancer amenable to local treatment after induction chemotherapy with epirubicin and cyclophosphamide or paclitaxel and cisplatin, depending on prior adjuvant chemotherapy, were enrolled. The median follow-up was 41 months (range, 7-85 months). PBSC were collected in 47 patients, and 40 received one or two courses of HDC. Local therapy was given in 37 patients. No treatment-related deaths occurred. Of 47 evaluable patients, 36 (75% of intention-to-treat population) had no evidence of disease or complete remission after completion of therapy. Six patients (12.5%) had partial response, two patients (4%) no change, and three patients (6%) progressive disease. The median time to progression and overall survival was 17.5 (95% confidence interval (CI), 14-21 months) and 42.2 months (95% CI, 33-52 months), respectively, and 27% of patients were progression free after 5 years. In conclusion, patients with oligometastatic breast cancer can be treated safely with this combined modality protocol with promising relapse-free survivals.

Adult↗
PubMed2003

Induction treatment before surgery for non-small cell lung cancer.

Surgery alone is currently still accepted "standard of care" for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large number of patients that present in these locally advanced stages. Enrollment of patients into ongoing prospective clinical trials should be encouraged, whenever possible, to further define prognostic factors and improve multimodality strategies in this clinical setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Prophylactic cranial irradiation as a component of intensified initial treatment of locally advanced non-small cell lung cancer.

Patients with locally advanced non-small cell lung cancer are threatened by the concurrent risks of local, regional and distant failure. By improving local and regional control with multimodality protocols, the brain becomes one of the major sites of relapse. PCI has a high potential to reduce the risk of brain metastases. Long-term toxicity is presently poorly defined and represents an important potential risk. The value of PCI as an adduct to present aggressive multimodality protocols and the optimal total dose with conventional fractionation will be investigated within clinical studies by two study groups in the future. As the best dose and fractionation still remains undefined, the integration of PCI into multimodality protocols.

Brain Neoplasms↗
PubMed2002

Dependence of the risk of encephalopathy on the radiotherapy volume after combined surgery and radiotherapy of invasive pituitary tumours.

The effectiveness of radiotherapy in reducing tumour recurrence of pituitary adenomas is well documented. On the other hand, the risk of side effects to the surrounding central nervous system normal tissue should not be underestimated. This retrospective study includes 58 patients with subtotally resected pituitary tumours. Photon from a 5,7 MV linear accelerator of a 60 cobalt unit with a source-isocenter distance of 80 cm were used throughout for treatment. The doses per fraction ranged from 45 Gy to 60 Gy. For a direct comparison of the different fractionation schedules, the biological effective total dose with 2 Gy per fraction was calculated for all the different application schemes with doses per fraction longer or smaller than 2 Gy. To do this, a fractionation sensitivity of the normal cerebral tissue by an square / square value of 2 Gy was assumed. Encephalopathy developed in 17 cases (28 percentage) after follow-up times of more than 5 years. Pathological CT- or MRI-findings were seen in 13 cases. Two factors were important for the genesis of radiogenic encephalopathy: 1. Multivariate analysis revealed that the risk of encephalopathy was associated with the radiation volume. 2. The location of the upper field border line was the strongest prognostic factor associated with the risk of encephalopathy (p<0.05).

Adolescent↗
PubMed2002

[Brachytherapy with (192)Iridium in the treatment of recurrent nasopharyngeal carcinoma].

BACKGROUND: Local recurrence of nasopharyngeal carcinomas can be treated in different ways. One option is re-irradiation e. g. as stereotactically guided convergent beam. An operative approach is possible in small recurrent tumours. Brachytherapy is a good alternative because of the steep dose gradient in the pre-irradiated area. METHODS: First step is the creation of a wide approach to the nasopharynx. This leads to a tumour mass reduction and gives space for the applicator. The radioactive substance will be brought into contact with the tumour by an afterloading procedure. The advantage of this therapy is the possibility to protect the surrounding tissue whereas the tumour receives a relatively high dosage. Between 2/90 and 12/96 10 men and 3 women were treated according to this protocol. RESULTS: The median age was 56 years (37- 66 years), the average follow-up period was 49,7 months (8 -123 months). 2 non keratinising and 11 undifferentiated carcinomas were treated. 5 of 13 patients were still alive at the end of the follow-up period. The 5 year over all survival rate was 46 %. 3 patients are free of disease for 5 years or longer. The patients were treated 2 to 6 times with 7 Gy in 5 mm depth. CONCLUSIONS: The results show that good palliation can be achieved by the applied method but larger studies are required to give a definite statement.

Adult↗
PubMed2002

Radiation-induced apoptosis in human non-small-cell lung cancer cell lines is secondary to cell-cycle progression beyond the G2-phase checkpoint.

PURPOSE: To characterize the relationship between cell-cycle progression and radiation-induced apoptosis in NSCLC cell lines with different p53 status. MATERIALS AND METHODS: Cell lines with functional (H460, A549) and non-functional p53 (H661 and H520) were irradiated with 20 Gy. Multiparameter flow-cytometry was used to follow the progression of synchronized cells through the cell cycle after irradiation. RESULTS: Delayed apoptosis was observed after cell-cycle progression beyond the G2 block, either in the late G2/M-phase of the same cell cycle being irradiated (H661, H520) or in the G1-phase of the subsequent cell cycle (H460, A549). The apoptotic fraction in H661 and H520 was 60-80% at 144h after irradiation, higher than in A549 and H460 (5 and 35%, respectively). As an alternative to apoptosis in cells cycling beyond the G2 restriction point, hyperploid cells were generated by all cell lines. Inhibition of cell-cycle progression through the G2/M-phase efficiently reduced the induction of late apoptosis. After irradiation in S-phase, 50-60% of cells with functional p53 remained arrested at the G2 restriction point until 144 h post-irradiation, while only 20% of the H661 or H520 did so. CONCLUSIONS: These data characterize radiation-induced apoptosis in NSCLC cell lines as a removal pathway of clonogenically inactivated cells secondary to cell-cycle progression beyond G2/M, and is unlikely to be a critical factor for cellular radiation sensitivity.

Apoptosis↗
PubMed2002

Induction chemotherapy followed by concurrent chemotherapy and definitive high-dose radiotherapy for patients with locally advanced non-small-cell lung cancer (stages IIIa/IIIb): a pilot phase I/II trial.

BACKGROUND: Overall prognosis of patients with locally advanced non-small-cell lung cancer (LAD-NSCLC) is still unfavourable. Different attempts to improve treatment results have been made using combinations of chemotherapy and radiotherapy. The aim of this pilot phase I/II investigation was to test the feasibility and toxicity of a definitive multimodality protocol in patients with irresectable NSCLC stages IIIA (N2) and IIIB. PATIENTS AND METHODS: Thirty LAD-NSCLC patients (stages IIIA/IIIB: 3/27; median age: 54 years, range 34-70; male/female: 17/13) who were consecutively enrolled onto our ongoing neoadjuvant multimodality protocol from October 1996 to February 1999 remained inoperable after induction treatment. Three cycles of cisplatin/etoposide (PE) were followed by hyperfractionated accelerated radiotherapy (HF-RTx: 1.5 Gy bid up to a total dose of 45 Gy in 3 weeks) concurrent with one cycle of PE. Definitive local treatment was completed with a small volume boost of 20 Gy (qd), adding up to a total dose of 65 Gy to the primary. Patients were routinely offered prophylactic cranial irradiation (PCI; 30 Gy; 2 Gy qd). RESULTS: Overall toxicity of the definitive CTx/RTx protocol-the main endpoint of this investigation-turned out to be acceptable (oesophagitis grade 3/4: 6/4 patients; pneumonitis grade 3/4: 0/1 patients; no treatment-related deaths). Actuarial survival at 2 years was 31% with a loco-regional control rate of 21%. CONCLUSIONS: This regimen turned out to be feasible with acceptable toxicity and will serve as a reference arm in a planned randomised trial in stage IIIB NSCLC, testing the value of surgery in this setting: preoperative induction CTx/RTx followed by surgery versus definitive CTx/RTx.

Adult↗
PubMed2001

Parametric oesophageal multiple swallow scintigraphy for validation of dysphageal symptoms during external beam irradiation of mediastinal tumours.

The aim of the study was to evaluate dysphageal symptoms and to measure the effect of local analgesic treatment using parametric oesophageal multiple swallow scintigraphy (PES) during external beam irradiation of the mediastinal region. Fifteen patients (most with lung cancer) with dysphagia grade II underwent PES during external beam radiotherapy of the mediastinum before and after application of local analgesics. Dynamic parametric condensed images were recorded. The intensity of clinical symptoms was correlated with the emptying rate at 10 s (ER-10 s) and the mean transit time (MTT). Visual analysis of the images was performed and the results were correlated with the fields of irradiation portals. Of the 15 patients, 12 showed a correlation between irradiation portals and the region of oesophageal motility disorder. Concordant results of clinical symptoms and PES data were found. In nine patients with a decrease in dysphagia following local analgesia, an increase in mean ER-10 s and a decrease in MTT were observed. In three patients with deterioration in clinical symptoms after analgesic treatment, a similar decrease in mean ER-10 s was found, though MTT remained constant. In three patients with normal values, motility disorders were detected in the dynamic study. In conclusion, PES was found to be a sensitive tool for the validation of dysphageal symptoms in patients during external beam irradiation of mediastinal tumours and for the evaluation and quantification of the efficacy of local analgesic treatment. Additional visual analysis of the dynamic study is helpful in diagnosing minimal disorders.

Adult↗
PubMed2001

Recombinant human erythropoietin increases the radiosensitivity of xenografted human tumours in anaemic nude mice.

PURPOSE: The effect of recombinant human erythropoietin (Epo) on the radiosensitivity of human tumour xenografts growing in anaemic nude mice was studied. METHODS AND MATERIALS: Anaemia was induced by total body irradiation (TBI) of mice prior to tumour transplantation. The development of anaemia was prevented by Epo (1000 U/kg s.c.) given 3 times weekly starting 2 weeks prior to TBI (5 Gy). Epo treatment did not influence the growth rate of the tumours, which were transplanted into the subcutis of the hind leg of mice. Thirteen days after TBI (tumour volume of approx. 40 mm3), a single-dose irradiation (12 Gy) of the tumour was performed resulting in a growth delay with subsequent regrowth of the tumours. RESULTS: In Epo-treated animals the tumour growth delay was significantly longer compared to anaemic mice. However, the radiosensitivity of tumours in non-anaemic animals' (non-Epo-treated) tumours could not fully be restored. CONCLUSION: These data give evidence for restored radiosensitivity after correction of anaemia with Epo.

Anemia↗
PubMed2001

Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in locally advanced nasopharyngeal carcinoma: a phase II study.

PURPOSE: The incidence of nasopharyngeal carcinoma in Germany is relatively low in comparison with certain regions in south-east Asia. However, standardised therapeutical regimes are required in the treatment of these tumours. METHODS: Between August 1990 and December 1997, 25 patients with stage III and IV nasopharyngeal carcinoma received an accelerated and hyperfractionated radiotherapy with concurrent chemotherapy (5-FU and mitomycin C). The primary tumour and positive lymph nodes received a total dose of 72 Gy over a period of 6 weeks. In the first 3 weeks, irradiation fields were treated five times per week with 2 Gy per fraction. Thereafter, treatment was accelerated, giving two daily fractions of 1.4 Gy. Salvage surgery was offered for residual lymph node disease after radiotherapy. RESULTS: The overall response rate defined as complete and partial response of the primary was 100%. Sixteen of the 25 patients were still alive and were free of any evidence of tumour recurrence or distant metastases at a mean follow-up period of 34 months (range 7-95 months). Six patients received salvage surgery. Only one of these six patients had histologically proven evidence of vital tumour. No severe late complications such as blindness or temporal lobe necrosis were observed. CONCLUSIONS: The presented data are promising and show that the combination of hyperfractionated accelerated radiotherapy and chemotherapy is feasible and effective.

Adult↗