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Michael Bamberg

Publications and source records attributed to Michael Bamberg.

At least 55 records · Page 3Linked to original sources
PubMed2003

Curative approaches to lung cancer in the elderly.

Lung cancer is a common disease in elderly patients, and the increase in the size of the elderly population will lead to an increased proportion of elderly among lung cancer patients in the future. The prognosis of lung cancer is still poor, but curative approaches are feasible for patients with local stage NSCLC and for some patients with limited disease (LD) SCLC. The evidence for these curatively-intended approaches is derived from studies that are usually performed with highly selected patients. Elderly patients are underrepresented, and in daily clinical practice elderly patients are less likely to be treated with full standard approaches. We used the data from studies that focused particularly on the elderly, or provided subgroup information on age, to analyze the feasibility of applying current standard approaches to the elderly. We also discuss alternative approaches. Age alone is a very uncertain prognostic criterion for outcome or tolerability of treatment. It is much more important to obtain a comprehensive geriatric assessment of each individual patient. When adequate patient selection is provided, standard treatment approaches appear to be feasible for elderly (>70 years) patients with good performance status.

Age Factors↗
PubMed2003

Hyperfractionated 192Ir brachytherapy for recurrent retroperitoneal sarcoma: a technique for delivery of local tumor boost dose.

BACKGROUND: Radical surgery is the treatment of first choice for retroperitoneal sarcoma. However, locoregional relapse is frequently observed leading to death in the majority of patients. The role of radiotherapy is not well defined in the management of retroperitoneal sarcoma. Yet, there is evidence that adjuvant irradiation does improve local tumor control. MATERIAL AND METHODS: In order to deliver sufficiently high radiation doses to the retroperitoneum, different techniques for application of a local tumor boost dose in addition to external beam treatment have been proposed. We present a technique of hyperfractionated (192)Ir brachytherapy (HFIR) of the tumor bed via intraoperatively implanted plastic catheters. Postoperative CT-based image-guided brachytherapy was performed. In two consecutive patients with recurrent retroperitoneal sarcoma, treatment was delivered twice daily with single doses of 1.5-2.0 Gy in 5-10 mm tissue depth up to a total dose of 18-32.5 Gy. RESULTS: HFIR of the tumor bed was easily accomplished facilitating delivery of high radiation doses to the retroperitoneum. No major late effects of treatment have been observed with a follow-up of 15 and 28 months, respectively. Details of the brachytherapy procedure are presented. CONCLUSION: HFIR via intraoperatively implanted catheters in the retroperitoneum is a technique suitable for application of a local tumor boost dose. Thus, sufficiently high doses of radiation mandatory for long-lasting local tumor control can be delivered in the tumor bed of the retroperitoneum without exceeding normal tissue radiotolerance in this unfavorable disease.

Brachytherapy↗
PubMed2003

Radiochemotherapy of malignant glioma in adults. Clinical experiences.

BACKGROUND: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. MATERIAL AND METHODS: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. RESULTS: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. CONCLUSIONS: Therefore, search for newer and more effective drugs continues, as well as for "optimal" administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation.

Adult↗
PubMed2003

[Death inducing ligands in combination with ionizing radiation: objective and current knowledge].

BACKGROUND: Apart from optimization of the radiation technology, future new strategies in radiation oncology will focus on the biological optimisation leading to improved adaptation of the tumor therapy on each tumor entity. In this regard, different areas of biological research may be distinguished: prediction, development of new cytotoxic agents, improvement of the tolerance of normal tissue and the optimisation of radiochemotherapy. MATERIAL AND METHOD: For the development of new strategies the knowledge of molecular mechanisms of radiation induced cell death is essential. In the present article a novel biological strategy for optimisation of radiotherapy is introduced. RESULTS: Distinct pathways mediate apoptosis in response to death receptor stimulation and ionizing radiation although an overlapping set of molecules is involved. TRAIL (TNF alpha-related apoptosis inducing ligand) is a type-II membrane protein belonging to the TNF family, which preferentially induces apoptotic cell death in a wide variety of tumor cells but not in normal cells. Based on the assumption of distinct signalling pathways, combination of TRAIL and ionizing radiation seems ideal to increase the therapeutic efficacy. Our study presents the rationale, own data, data of other groups as well as the current status of the latest findings regarding the function and physiological role of the TRAIL death ligand. CONCLUSIONS: Apoptosis resistance towards ionising radiation is not associated with a general apoptosis resistance. Death ligands, for example TRAIL trigger apoptosis even in cells not undergoing apoptosis in response to radiation. A combination of both modalities induces additive or synergistic effects in regard to apoptosis induction and eradication of clonogenic tumor cells. Thus, the combination of TRAIL with radiation proofs that novel treatment strategies may be developed on the basis of molecular or cell biological research.

Animals↗
PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity.

BACKGROUND: For more than 60 years, radiation therapy has been an integral part in the management of childhood low-grade glioma. As this tumor carries an excellent long-term prognosis, the risk of late effects is of particular clinical importance and impinges upon radiotherapeutic treatment strategies. MATERIAL AND METHODS: Studies on the use of radiation therapy in children with low-grade glioma were systematically reviewed for data on radiotherapy-induced side effects on brain parenchyma, endocrine dysfunction, growth retardation, neurocognitive dysfunction, vasculopathy, and secondary neoplasms. RESULTS: Data on late effects are scarce and heterogeneous. Past reports included only retrospective series from the 1930s to present days, a time during which treatment policies and radiation techniques widely varied and considerably changed in recent years. Often, considerable uncertainty existed regarding pretreatment health status and radiotherapy-related factors (e.g., total dose, dose per fraction, treatment fields). In spite of these shortcomings and often conflicting observations, it appears that especially younger children and children with neurofibromatosis (NF) are at risk of endocrinopathies in terms of growth retardation and developmental abnormalities, as well as neurocognitive dysfunction expressed as problems in the psychosocial environment such as in education and occupation. However, both observations may be attributed to the higher proportion of NF in the very young who frequently develop large tumors spreading along the entire supratentorial midline. The risk of radiation-induced disturbances in visual function is low (no case reported). Young children with NF appear to have an increased risk of vasculopathies. 33 cases of moyamoya disease were found (preferably in the very young), 18 of whom were NF-positive. Other cerebrovascular accidents (24 cases, of whom 14 were NF-positive) and secondary neoplasms (15 cases, of whom only five occurred in field--four were high-grade astrocytomas) are a rare condition. The latter cannot be distinguished from late relapses with malignant transformation. Modern treatment techniques appear to reduce the risk of radiation-induced late effects. CONCLUSIONS: More studies and clear definitions of clinical endpoints such as neurocognitive and endocrinological outcome are needed in order to clarify the impact of radiation therapy on the risk of late sequelae. Presently, the strategy to postpone radiotherapy in the younger children, especially with NF, is justified to reduce the risk of late effects. These information and the contribution of tumor, surgery and chemotherapy will help to define the role of radiation therapy in the future management of childhood low-grade glioma and whether the use of highly sophisticated and expensive treatment techniques is justifiable. The recently initiated prospective study of the APRO (Pediatric Radiooncology Working Party) on documentation of dose prescription to organs at risk and the network of the GPOH to explore late effects as well as the forthcoming prospective SIOP/GPOH (International Society of Pediatric Oncology/German Society of Pediatric Oncology and Hematology) LGG 2003 trial are addressing these issues.

Adolescent↗
PubMed2003

Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I: Treatment modalities of radiation therapy.

BACKGROUND: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented. RESULTS: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups. CONCLUSIONS: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Adolescent↗
PubMed2003

Treatment of lung cancer in the elderly. Part I: non-small cell lung cancer.

There is a general trend worldwide of an increasing incidence of elderly population. Age is the greatest risk factor for cancer; therefore, this demographic shift is the main reason for an increase of cancer incidence. Lung cancer is a typical disease of the elderly patients. This review summarizes the issues of treatment of non-small cell lung cancer (NSCLC) in the elderly. Early stage NSCLC is usually treated with radical surgery, locally advanced NSCLC with radiotherapy (RT) and/or chemotherapy (CHT) and metastatic disease with CHT, but the evidence for these approaches is based on studies which are usually performed with highly selected patients while elderly patients are under-represented. We used the data from studies addressing particularly elderly or providing subgroup information on age to analyse the feasibility of current standard approaches for elderly and discuss alternative approaches. Surgery is an effective method in elderly patients with early stage NSCLC although some approaches bear a somewhat higher risk of operative morbidity and mortality. RT for early stage may be an alternative with curative potential. For locally advanced stage RT alone, or combined radiochemotherapy in selected cases, is feasible for elderly patients with locally advanced NSCLC when a careful assessment of pre-therapeutic status is made and appropriate drugs are selected. Advanced age alone also should not preclude CHT, although the risk of adverse effect may be higher in certain cases. New generation drugs seem to be particularly feasible and efficient in elderly patients. In general, age itself does not seem to preclude patients from standard treatments although in some cases co-morbidity forces to alternative approaches. Currently, single-agent CHT should be considered as the standard treatment of advanced NSCLC elderly patients.

Age Factors↗
PubMed2003

Treatment of lung cancer in elderly part II: small cell lung cancer.

There is a general trend worldwide of an increasing incidence of elderly population. Age is the greatest risk factor for cancer; therefore, this demographic shift is a main reason for an increase of cancer incidence. Lung cancer is a typical disease of the elderly patients. Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancer cases. This review summarises the issues of treatment of SCLC in elderly. The number of randomised phase III trials concerning treatment of SCLC in elderly patients are very limited. Although currently most treatment decisions are based on lower grades of evidence, some conclusions can be drawn from the current studies. Age alone is a very uncertain prognostic criteria for outcome or tolerability of treatment. Much more important is the geriatric assessment of each individual patient. Current treatment standards for limited disease (LD)-SCLC (polychemotherapy plus local thoracic irradiation and additional prophylactic cranial irradiation in case of complete remission) seems to be also feasible for 'fit' elderly (>70 years) LD-SCLC patients with a good performance and full functional capacities. There are preliminary data indicating that a similar outcome in elderly patients can probably be achieved a with reduced number of treatment schedules (e.g. 2 instead of 4 cycles in combination with radiotherapy. Surgical resection is also feasible in selected elderly patients with very early stage SCLC, where this maybe an appropriate approach, although no phase III data are available, which demonstrated the benefit of additional surgery compared to chemotherapy alone in early stage SCLC. In patients with extensive disease-SCLC age alone does not necessarily restrict the use of multiagent regimen, although the risk of haematological toxicity seems to be higher than in the younger patients. When standard treatment is not feasible due to co-morbidity or loss of functional capacity, several alternative combination regimens are available, which appear to be slightly superior to single agent treatment, although randomised data for elderly on that issue are sparse. Carboplatin and etoposide seems currently the most appropriate two-drug combination in elderly patients, but there are a variety of active and low toxic third generation agents like taxanes, gemcitabine and vinorelbine which are active in both, non-small cell lung cancer and SCLC. For the comparison of trials in elderly patients it will be of key importance to include a comprehensive and standardised geriatric assessment in such studies.

Aged↗
PubMed2003

Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning.

Allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning was evaluated in 22 patients (median age 53, range 36-66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)-identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA-mismatched unrelated donor]. Graft-versus-host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) (n = 12) or CSA plus mycophenolate mofetil (n = 10). Despite of heavy pretreatment, the transplant-related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2-19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8-36 months) post allografting. Estimated 2 year overall and event-free survival was, respectively, 25.5% and 22.0% for the whole patient group, and 62.5% and 57.1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation (P = 0.0182) and absence of cGVHD (P = 0.069) were associated with shorter event-free survival. Thus long-term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.

Acute Disease↗
PubMed2003

Novel chemotherapeutic agents for the treatment of glioblastoma multiforme.

During the last few decades, the discovery of novel targets for therapeutic intervention led to the development of chemotherapeutic agents that specifically interfere with altered cellular functions of tumour cells. Genetic alterations in glioblastoma affect cell proliferation and cell cycle control, as well as invasive and metastatic growth. Therefore, innovative therapeutic strategies have been based on drugs targeting cellular proliferation, invasion, angiogenesis, metastasis and differentiation of tumour cells. Furthermore, disruption of cell-death pathways also contributes to the pathogenesis of glioblastoma and may result in resistance to chemotherapy and radiation. Therefore, additional treatment strategies that target intracellular survival and/or apoptotic pathways are under current laboratory investigation. The progress in the understanding of glioblastoma tumour biology and the refined diagnosis of individual patients together with the exploration of targeted drugs may allow a risk-adapted, individualised therapeutic strategy and will hopefully improve prognosis of glioblastoma patients in the future.

Angiogenesis Inhibitors↗
PubMed2003

Hypoxic radiosensitizers and hypoxic cytotoxins in radiation oncology.

Tumor hypoxia is a major constraint for the tumor treatment by radiotherapy. The efficacy of ionizing radiation directly relies on adequate oxygen tensions. Furthermore, hypoxia is related to malignant progression, increased invasion, angiogenesis and an increased risk of metastases formation. Two different types of strategies can be used to overcome the problem of hypoxia-mediated radioresistance. The first strategy encompasses a variety of different methods to improve the tumor oxygenation during radiotherapy. The second strategy tries to target hypoxia as a relatively unique feature of tumor tissue by means of drugs, which are activated under hypoxic conditions and act as hypoxic radiosensitizers or hypoxic cytotoxins. This article reviews in brief the clinical experience with different generations of hypoxic radiosensitizers and hypoxic cytotoxins, which have been applied in combination with primary radiotherapy during the last three decades.

Animals↗
PubMed2002

Stereotactic fractionated radiotherapy in patients with optic nerve sheath meningioma.

PURPOSE: To evaluate the effectiveness of stereotactic fractionated radiotherapy (SFRT) in the treatment of optic nerve sheath meningioma (ONSM). METHODS AND MARERIALS: Between 1994 and 2000, a total of 39 patients with either primary (n = 15) or secondary (n = 24) ONSM were treated with SFRT and received a median total tumor dose of 54 Gy using 1.8 Gy/fraction. RESULTS: The radiographic response to SFRT was documented in all patients as stable disease (no change) except for 1 patient with a partial response. After a median follow-up of 35.5 months, all patients with ONSM were alive without recurrence. The visual fields and visual acuity were improved in 6 of 15 and 1 of 16 examined eyes in patients with primary ONSM, respectively, and in 6 of 24 and 7 of 26 examined eyes in patients with secondary ONSM, respectively. Stable visual fields and visual acuity was observed in 8 of 14 and 15 of 16 patients with primary ONSM, respectively, and in 17 of 24 and 19 of 26 patients with secondary ONSM, respectively. Except for reversible alopecia and erythema, no other SFRT-related toxicity was observed. CONCLUSION: SFRT represents a very effective and low-toxic treatment modality for ONSM. Despite a median follow-up of 3 years, this series of primary ONSM holds promise for future studies. It adds substantial evidence that SFRT may definitely become a standard treatment approach in selected cases of ONSM.

Adolescent↗
PubMed2002

Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer.

PURPOSE: To investigate the effectiveness of high-dose, curative radiotherapy (RT) given alone in technically operable, but medically inoperable, patients with early-stage (I-II) non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Computerized and manual searches were done to identify published reports dealing with curative RT for NSCLC. Relevant studies were identified and the information provided therein was extracted regarding patient and treatment characteristics, treatment outcome, and various pretreatment and treatment-related factors influencing outcome, as well as toxicity and quality-of-life issues. RESULTS: Although a large variation of pretreatment and treatment characteristics was noted in the available studies, a median survival time of >30 months and a 5-year survival rate of up to 30% had been achieved. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation, or its equivalent when altered fractionation is used, are necessary for control of NSCLC. Smaller tumors seem to have a favorable prognosis, and the issue of elective nodal RT continues to be controversial. Analyses of patterns of failure have clearly identified local failure as the predominant pattern. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influence survival. Toxicity was usually low, but very high doses (e.g., 80 Gy) given with a conventional approach may carry a risk of an excessive rate of side effects. CONCLUSION: High-dose, curative RT is an effective treatment modality in technically operable, but medically inoperable, patients with early-stage NSCLC.

Aged↗
PubMed2002

Effect of gemcitabine on acute and late radiation toxicity of skin and underlying soft tissues to single-dose irradiation in a nude mice model.

PURPOSE: To investigate the influence of gemcitabine (GEM) on acute and late toxicity of radiotherapy (XRT) in an in vivo model of acute skin reactions and late fibrotic sequelae of skin and underlying soft tissues. METHODS AND MATERIALS: Single-fraction XRT was applied to the right hind leg of nude mice under ambient conditions. Single-dose GEM was applied i.p. (550 mg/kg body weight). In a first set of experiments, the influence of timing of chemotherapy relative to the onset of irradiation was investigated with GEM application 36, 24, and 2 h before and 24 h subsequent to 40 Gy XRT. With a fixed interval between chemotherapy and XRT taken from these studies, the dose-response relationship was examined for XRT in the range of 20-65 Gy. Control mice were irradiated without GEM treatment. Using a scoring system, onset, duration, and extent of acute skin reactions were analyzed. Skin fibrosis was measured by intracutaneous ink-mark separation. Soft tissue fibrosis was assessed using the leg contracture assay. ED50 calculations were performed for extent of acute and late reactions. RESULTS: Timing of GEM application relative to XRT had no significant influence on acute skin reactions or on fibrotic changes. Onset, duration, and extent of acute skin toxicity, as well as skin and leg contracture, were not significantly modulated by GEM in the dose-response experiments with GEM applied 2 h before XRT. CONCLUSIONS: Acute and late toxicity of skin and underlying soft tissues is not significantly increased after single-fraction radiotherapy in combination with GEM in the nude mice model.

Animals↗
PubMed2002

Elective neck irradiation in locally advanced squamous cell carcinoma of the maxillary sinus: a review.

This review has been undertaken to evaluate the impact of elective nodal irradiation (ENI) in locally advanced squamous cell carcinoma (SCC) of the maxillary sinus. The indications for radiotherapy (RT) including the dose, the volume to be covered, as well as possible toxicities encountered in the reports available are discussed. A total dose of 50 Gy standard fractionation appears to be efficient in achieving locoregional control in about 95% of all cases with low toxicity. The lymphatic drainage that needs to be covered remains to be defined more clearly, but it seems that there is no need for irradiation of the low neck. Bilateral upper neck irradiation remains controversial. Pattern of nodal failure in patients who received ENI and in those without ENI seem to suggest ipsilateral neck irradiation confined to submandibular and subdigastric/jugulodigastric areas. Finally, matching of the primary (maxillary sinus) tumor fields and neck field(s) must be carefully performed so as not to leave regions of possible under/overdosage of these neck areas. The authors believe that ENI is justified in these patients. However, given the background of only a few studies addressing this issue and anticipated better local control with the newer technologies, this issue needs to be properly studied in the future.

Carcinoma, Squamous Cell↗
PubMed2002

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.

Adolescent↗
PubMed2002

Antineoplastic effects of chemotherapeutic agents are potentiated by NM-3, an inhibitor of angiogenesis.

Antiangiogenic therapy, although effective in shrinking tumors, has not yet been established as a standalone treatment for cancer. This therapeutic limitation can be overcome by combining angiogenesis inhibitors with chemotherapeutic agents. NM-3, a small molecule isocoumarin, is a recently discovered angiogenesis inhibitor. Here we demonstrate that NM-3 inhibits the proliferation of human umbilical vein endothelial cells in vitro, at concentrations 10-fold less than those required to inhibit normal fibroblasts or tumor cells (HT29, MKN28, and MCF-7). NM-3 alone inhibits endothelial sprouting and tube formation in vitro. The results also show that synergistic antiproliferative activity is observed when human umbilical vein endothelial cells are treated with NM-3 in combination with 5-fluorouracil. The effects of treatment with NM-3 and various chemotherapeutic agents were also evaluated in tumor xenografts. The results demonstrate that combined treatment with NM-3 and chemotherapeutic agents significantly reduced mean tumor volume compared with either treatment alone, with no effects on body weight changes. Taken together, these findings demonstrate that NM-3 is a well-tolerated angiogenesis inhibitor that significantly increases the efficacy of existing antineoplastic agents.

Angiogenesis Inhibitors↗