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C Nieder

Publications and source records attributed to C Nieder.

At least 19 recordsLinked to original sources
PubMed2003

Influence of differing radiotherapy strategies on treatment results in diffuse large-cell lymphoma: a review.

In the absence of evidence from randomised trials, radiation treatment of diffuse large-cell lymphoma of B-cell type represents an area of controversy with considerable differences in patterns of practice. The present literature survey aims at clarification of the role of radiotherapy in combined modality settings by identification of dose-response relationships, predictive factors for local control, and potential pitfalls in the interpretation of retrospective studies. Radiotherapy might increase local control in initially involved areas and is usually delivered to these sites (involved-field treatment). Combined modality treatment is currently recommended for patients in stage I or II if they are not treated in the context of prospective studies. Whether involved-field consolidation radiotherapy after systemic treatment in patients with bulky, stage III-IV lymphomas should be routinely recommended is presently unclear. Definition of bulky disease is arbitrary and varied between 6 and 10cm, reflecting a considerable difference in the number of clonogenic tumour cells. Several retrospective and one prospective randomised study suggest improved disease-free and overall survival by radiotherapy in advanced stages. The 5-year local control by radiotherapy was 93-98%. Currently, we recommend the following minimum doses for involved-field radiotherapy derived from this literature survey. Lymphomas with initial size <3.5 cm (possibly <6 cm) can be treated with 30 or 30.6Gy when a complete remission (CR) has been achieved by chemotherapy. The next group might be sufficiently controlled by 36Gy, but it remains unclear whether the cut-off should be 6cm or higher. Forty Gy appears to control tumours in the range of 7-10cm. Most likely, 45Gy does not have to be exceeded for larger lesions. Data on those with less than CR are contradictory. Judging the amount of viable tumour in these patients is problematic, but crucial to determine the intensity of further treatment. The value of positron emission tomography is still under investigation. Because the difference between doses of 30 and 40Gy might actually make a difference for the long-term toxicity of radiotherapy in some of the normal tissues and organs at risk (salivary glands, orbital structures, lung, heart, etc.), it appears prudent to resolve the open questions in prospective trials with careful documentation of side effects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Report of a male patient with brain metastases from breast cancer.

As in female patients, the clinical course in male patients with breast cancer is determined mainly by tumor stage. The literature contains very limited data on either the occurrence or the treatment of CNS metastases. This paper presents the case report of a 69-year-old man with multiple brain metastases 7 years after a diagnosis of lymph-node positive breast cancer, which had earlier already spread to the bones and liver. Whole-brain irradiation with a total dose of 30Gy resulted in palliation of symptoms. Nevertheless, survival was very short (7 weeks from diagnosis). Patients with metastatic breast cancer are at risk for the development of brain metastases. When performance status is poor the survival of patients with brain metastases is very limited. Treatment recommendations are the same as those for female patients with brain metastases from breast cancer.

Aged↗
PubMed2001

Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple?

PURPOSE: To review the value of extended diagnostic work-up procedures and to compare the results of comprehensive or volume-restricted radiotherapy in patients presenting with cervical lymph node metastases from clinically undetectable squamous cell carcinoma. METHODS AND MATERIALS: A systematic review was undertaken of published papers up to May 2000. RESULTS: Positron emission tomography (PET) has an overall staging accuracy of 69%, with a positive predictive value of 56% and negative predictive value of 86%. With negative routine clinical examination and computerized tomography (CT) or magnetic resonance imaging (MRI), PET detected primary tumors in 5-25% of patients, whereas ipsilateral tonsillectomy discovered carcinoma in about 25% of patients. Laser-induced fluorescence imaging with panendoscopy and directed biopsies showed some encouraging preliminary results and warrants further study. All together, the reported mucosal carcinoma emergence rates were 2-13% (median, 9.5%) after comprehensive radiotherapy and 5-44% (median, 8%) after unilateral neck irradiation. The corresponding nodal relapse rates were 8-45% (median, 19%) and 31-63% (median, 51.5%), and 5-year survival rates were 34-63% (median, 50%) and 22-41% (median, 36.5%), respectively. Retrospective single-institution comparisons between comprehensive and unilateral neck radiotherapy did not show apparent differences in outcome. Prognostic determinants for survival are the N stage, number of nodes, extracapsular extension, and histologic grade. No data were found to support the benefit of chemotherapy in this disease. CONCLUSION: Physical examination, CT or MRI, and panendoscopy with biopsies remain the standard work-up for these patients. Routine use of PET or laser-induced fluorescence imaging cannot be firmly advocated based on presently available data. Although combination of nodal dissection with comprehensive radiotherapy yielded most favorable results, its impact on the quality of life should be recognized, and the confounding effects of patient selection for various treatment modalities on therapeutic outcome cannot be ruled out. A randomized trial comparing the therapeutic value of comprehensive vs. volume-limited radiotherapy is being considered.

Biopsy↗
PubMed2001

The results of colorectal cancer treatment by p53 status: treatment-specific overview.

PURPOSE: Both negative and positive influences of mutant p53 on treatment outcome have been reported, and we present here a meta-analysis of published studies where outcome was reported for defined treatment groups. METHODS: We identified articles on the effect of p53 status by treatment modality, excluding those not stratified by method of treatment. A common hazard ratio was estimated from studies that reported a multivariate analysis. We also estimated the numbers of patients expressing the endpoint at the mean or median follow-up time and calculated a pooled odds ratio. RESULTS: Twenty-eight articles were evaluable (23 using immunohistochemistry to detect overexpression of p53 and 8 using DNA sequencing), for a total of 4,416 patients. For patients treated with surgery only, the immunohistochemistry studies showed a significant influence of p53 status on disease-free survival and a marginally significant influence on overall survival. In the studies using DNA sequencing, by contrast, there was a significant influence of p53 mutations on overall survival, but not disease-free survival. For patients treated with surgery and radiotherapy, the influence of p53 status on disease-free survival was either insignificant or marginally significant, depending on test used; there was no influence on overall survival. CONCLUSIONS: Although this pooled analysis of published studies where treatment was accounted for shows that there is a borderline significant hazard associated with p53 overexpression or mutation vs. p53 wild-type, it is unlikely that p53 can be applied in a routine clinical setting alongside factors such as T stage, nodal status, and residual tumor, whose prognostic value is much stronger.

Adenocarcinoma↗
PubMed2001

[Stereotactic radiation therapy with a modified linear accelerator in patients with brain metastases].

UNLABELLED: The aim of the study was to analyze the results of stereotactic radiotherapy using a linear accelerator in patients with brain metastases. We quantified the following clinical parameters: tumor response and tumor control after therapy, survival, and side effects. Results of the treatment were compared with those from traditional treatment strategies such as surgery and whole brain irradiation. Sixty patients with brain metastases (80 lesions, 36 men and 24 women, mean age 57 years) were treated with stereotactic radiotherapy. The mean follow-up time was 13 months. CONCLUSION: Stereotactic radiotherapy is an important option in the treatment strategy for patients with brain metastases. In comparison to whole brain irradiation, stereotactic radiotherapy achieved a higher local tumor control with a lower rate of side effects. In comparison to surgery, stereotactic radiotherapy has the advantages of shorter treatment time and lower treatment-related morbidity and mortality.

Adult↗
PubMed2001

The challenge of p53 as prognostic and predictive factor in Hodgkin's or non-Hodgkin's lymphoma.

The results of individual studies examining the role of p53 as a predictive and prognostic factor in lymphoid malignancies have varied considerably. In order to summarize the available data on the overexpression or mutation of p53 in Hodgkin's and non-Hodgkin's lymphoma, a systematic literature review was performed. Twenty-four studies met the eligibility criteria. With respect to non-Hodgkin's lymphoma, most studies seem to support the hypothesis that patients whose tumors contain wild-type p53 respond better to treatment and have increased survival rates. If true, the implication may be that patients with p53 mutated tumors could be selected for non-standard treatment. With respect to Hodgkin's lymphoma, comparable associations were rarely reported. However, techniques for assessing the inactivation of p53 varied widely. Furthermore, in most instances, the study design and/or statistical methods did not allow sufficient analyses of the influence of confounding factors such as histologic type, stage, first-line and salvage treatment, etc. Therefore, it remains unclear whether the apparent influence of p53 status on outcome in non-Hodgkin's lymphoma is independent of established parameters such as stage, performance status, etc. Further studies involving large numbers of specimens derived from patients treated in clinical trials with identical regimens, follow-up and salvage strategies are needed. These studies should also be stratified according to histologic subtypes.

Disease-Free Survival↗
PubMed2000

A palliative accelerated irradiation regimen for advanced non-small-cell lung cancer vs. conventionally fractionated 60 GY: results of a randomized equivalence study.

PURPOSE: Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find out if there is a substantial difference in outcome between these approaches, we performed a randomized prospective study. METHODS AND MATERIALS: Between 1994 and 1998, 152 eligible patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31) were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and mediastinum. RESULTS: One-year survival rate for all patients was 37% with no significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76). As far as can be judged from limited data available, palliation was adequate and similar for the two treatment arms. Apart from expected differences in the time course of esophagitis, acute side effects were moderate and equally distributed. No severe late effects were observed. CONCLUSIONS: In the present randomized trial, survival and available data on palliation were not different after cf to 60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are not suitable for radical treatment approaches, the prescription of a palliative short-term irradiation appears preferable compared to cf over several weeks.

Adenocarcinoma↗
PubMed2000

Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes?

PURPOSE: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. METHODS: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) <70% and KPS > or =70%, as proposed by the RTOG. RESULTS: Median overall survival was 2.9 months (2.0 months for patients with KPS <70% and 3.6 months for patients with KPS > or =70%, p < 0.001). We did not find other variables splitting patients with KPS <70% in different prognostic groups. However, advanced age, multiple brain metastases, presence of extracranial metastases, and uncontrolled primary tumor each predicted shorter survival in patients with KPS > or =70%. When grouped into the original RTOG RPA classes, our data set split into three subgroups with different prognosis and median survival times of 10.5, 3.5, and 2 months, respectively (p < 0.05). Only 3% of patients fell into the most favorable group. Median time to non-CNS death was 4.1 months (12.9 months in RPA class I, 4.9 months in RPA class II, and 3.8 months in RPA class III, respectively, p > 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS > or =70%. In patients with KPS <70%, no statistically significant prognostic factors were identified for this endpoint. CONCLUSIONS: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases.

Adult↗
PubMed2000

A review of current and future treatment strategies for malignant astrocytomas in adults.

BACKGROUND: For more than 20 years, after establishing the role of postoperative radiotherapy for malignant astrocytomas, no definitive improvement in survival rates could be observed, despite advances in established treatment modalities such as radiotherapy and chemotherapy. This review discusses available laboratory and clinical data as well as recent advances in our knowledge about prognostic factors (Table 1) and their implications for the design of future clinical trials. RESULTS: Elucidation of the biology of malignant astrocytomas allowed for development of rational new approaches, such as gene therapy and immunotherapy, which could interfere with established treatment regimens or being used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called suicide genes. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or O6-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C, and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro. CONCLUSIONS: Several rational new approaches are now entering clinical trials (Table 2). In the light of limited survival after standard treatment it is recommended that patients should be offered participation in such trials.

Adult↗
PubMed2000

The challenge of p53 as prognostic and predictive factor in gliomas.

In recent years, increasing interest in genetic abnormalities and biologic factors such as the tumour suppressor gene p53 as possible predictive and prognostic factor in gliomas has emerged. Inactivation of p53 can result in resistance to apoptosis, one of the mechanisms thought to explain the failure to respond to DNA-damaging agents. Thus, inactivation of p53 might be associated with a worse prognosis. Considering the inconsistent results of several recent studies, it has remained controversial whether p53 actually can be related to response to treatment and patients' prognosis. Therefore, a systematic review of the literature was performed, which included 28 publications. Techniques for assessing the inactivation of p53 varied widely. Overall, approximately 50% or more of astrocytoma specimens evaluated by immunohistochemistry stained positively for p53, regardless of histologic grade. Eight studies were restricted to comparably treated patients within a single histologic group. In most instances, non-restrictive inclusion criteria and use of statistical methods, which were not sufficient to correct the possible bias, make it difficult to reach unequivocal conclusions. However, it appears that the prognostic information of p53 is at best marginal, especially when compared to established parameters such as grading, age, etc. Its predictive value, which most likely is rather limited too, can hardly be judged without prospective studies also evaluating other biological factors as well as end-points other than time to radiological progression.

Astrocytoma↗
PubMed2000

A comparison of treatment results for recurrent malignant gliomas.

Retreatment of malignant gliomas may be performed with palliative intent after careful consideration of the risks and benefits, and with special regards to iatrogenic neurotoxicity and quality of life (QOL). This review compares studies of several retreatment strategies (published between 1987 and 2000) based on the quality of their evidence. Depending on both established prognostic factors and previous treatment, individually tailored retreatment strategies are possible. In all studies that included a multivariate analysis of prognostic factors, performance status was the most important. So far, predictive factors for response, which might facilitate patient selection, have not been unequivocally defined. In terms of QOL, single-agent chemotherapy (temozolomide, nitrosoureas, platinum and taxane derivatives) may offer a better therapeutic ratio than polychemotherapy. For glioblastoma multiforme, progression-free survival and QOL were more favourable after temozolomide than procarbazine (level 1 evidence). The survival of patients after various radiotherapy techniques is broadly similar. However, considerable toxicity is associated with radiosurgery or brachytherapy. Fractionated stereotactic radiotherapy plus radio-sensitizing cytostatic agents has shown promising initial results in small groups of selected patients and awaits further evaluation. Level 2 evidence derived from non-randomized studies does not suggest a substantial prolongation of survival by re-resection as compared with chemotherapy or radiotherapy alone. Level 1 evidence derived from a randomized trial suggests that application of BCNU polymers significantly improves the outcome after re-resection. However, most studies reported median survival in the range of only 25-35 weeks, thereby emphasizing the need for the development and clinical evaluation of new innovative treatment approaches.

Adult↗
PubMed2000

Tissue tolerance to reirradiation.

There are increasing requests for delivering a second course of radiation to patients who develop second primary tumors within or close to previous radiotherapy portal or late in-field recurrences. Rational treatment decisions demand rather precise knowledge on long-term recovery of occult radiation injury in various organs. This article summarizes available experimental and clinical data on the effects of reirradiation to the skin, mucosa, gut, lung, spinal cord, brain, heart, bladder, and kidney. The data reveal that, in general, acutely responding tissues recover radiation injury within a few months and, therefore, can tolerate another full course of radiation. For late toxicity endpoints, however, tissues vary considerably in their capacity to recover from occult radiation damage. The heart, bladder, and kidney do not exhibit long-term recovery at all. In contrast, the skin, mucosa, lung, and spinal cord do recover subclinical injury partially to a magnitude dependent on the organ type, size of the initial dose, and, to a lesser extent, the interval between radiation courses. The available clinical data have inspired many radiation oncologists to undertake systematic studies addressing the efficacy and toxicity of reirradiation in various clinical settings. Hopefully, systematic scoring, collection, and analysis of patient outcome will produce quantitative data useful for clinical practice.

Animals↗
PubMed2000

Dose-response relationships for radiotherapy of brain metastases: role of intermediate-dose stereotactic radiosurgery plus whole-brain radiotherapy.

The effects of intermediate-dose radiotherapy consisting of whole-brain radiotherapy (WBRT, 10 fractions of 3 Gy) plus stereotactic radiosurgery (SRS) were studied prospectively. Twenty-five adult patients with 31 brain metastases received WBRT plus linear accelerator (LINAC)-based single dose SRS with fixed treatment parameters (10 Gy at the isocenter, target volume enclosed by the 90% isodose). Median age was 63 years, median Karnofsky performance status 80%, and median diameter of brain metastases 2.4 cm. Fifteen patients had non-small-cell lung cancer. Because of some early deaths, only 26 lesions could be evaluated for response. We observed 1 complete and 15 partial remissions. Median time to progression inside or outside the SRS volume was 4.5 months. Actuarial local control of SRS-treated lesions was 61% at 1 year. At that time, only 37% of patients were free from new lesions outside the SRS volume. Median survival and cause-specific survival were 2.3 and 4.5 months, respectively (1-year survival rate 8% and 21%). Ten patients died of progressive brain metastases, 13 from extracranial disease progression (unknown cause of death in 2 cases). Comparable to SRS studies with higher doses, the majority of brain failures occurred outside the SRS volume and more patients died of extracranial progression than of uncontrolled brain metastases. Failure to improve survival can be explained by the high percentage of patients with extracranial metastases (52%). However, the present results appear less favorable than those of previous studies of SRS with 15 Gy to 16 Gy (1-year actuarial local control rates of 66-89%). Therefore, we recommend SRS with 15 Gy to 16 Gy for patients whose favorable prognostic factors justify a boost after WBRT.

Adult↗
PubMed1999

18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis.

PURPOSE: 18F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. METHODS AND MATERIALS: Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. RESULTS: In 12/34 cases, the shape and/or size of the portals were changed, primarily (n = 10) the size of the fields was reduced. The median area of CP was 182 cm2 versus 167 cm2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p = 0.03). CONCLUSION: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particularly for patients with tumor-associated dys- or atelectasis.

Carcinoma, Non-Small-Cell Lung↗