Biomedical subjects

Wilfried Budach

Publications and source records attributed to Wilfried Budach.

34 records · Page 2Linked to original sources

PubMed2004

On the actual state of industrial quality assurance procedures with regard to (106)Ru ophthalmic plaques.

BACKGROUND: In radiotherapy of intraocular tumors, e. g., in the case of malign choroid melanomas, episcleral brachytherapy with (106)Ru ophthalmic plaques has proven to be successful. In a study, the authors reported on the discovery of the following shortcomings in industrial quality assurance, which are relevant to therapy, during the course of an internal clinical acceptance test of (106)Ru ophthalmic plaques, manufactured by the company Bebig from Berlin, Germany. This consisted of inconsistent dose rate specifications in the manufacturer's certificate, covering a range of 111% and with the risk of leakage of the plaques. Bebig was called upon to adapt state-of-the-art production methods with regard to (106)Ru ophthalmic plaques. MATERIAL AND METHODS: In the meantime, Bebig has modernized production of (106)Ru ophthalmic plaques and adopted all the quality assurance procedures proposed by the authors. Moreover, the requested traceability of the calibration of activity and dose rate of the (106)Ru ophthalmic plaques to standards of the federal authorities in charge of measurement procedures has been implemented. RESULTS: In the year 2002, Bebig updated, among other things, the ASMW (GDR) calibration of the dose rate of the (106)Ru ophthalmic plaques from the years 1987-1989 by a calibration of the NIST (USA). The current NIST calibration, together with the new equipment for the measurement of the depth dose curves, led to the consequence that the new NIST 2001 dose rate values show, in the mean, a deviation of 0.75 times (plaque type CCC) up to 2.06 times (plaque types CCX, CCY, and CCZ) compared to the dose rate values that had been indicated so far in Bebig's certificate, based on the ASMW 1987 calibration. For the 95% confidence interval, Bebig estimated the measurement uncertainty to be +/- 25%. If one takes into consideration the minimal and maximal values in such 95% confidence intervals, it follows that the new NIST 2001 dose rate values deviate between 0.56 times (plaque type CCC) and 2.58 times (plaque types CCX, CCY, and CCZ) from the Bebig certificate (ASMW calibration 1987). As regards leakage, no objections arose in the case of the (106)Ru ophthalmic plaques produced according to the new quality standards. CONCLUSION: Legislation has to make sure that the use of radioactive material on humans be, among other things, permitted as a matter of principle only, if the dose rate calibration can be traced to standards of a federal authority of measurement procedures. Furthermore, special leakage tests for radiation sources which come into direct contact with body fluids should be established. A historical retrospect reveals that the greatest changes have taken place in the indication of the dose rates of (125)I sources. Since the beginning of the use of (125)I sources in brachytherapy in the late 1960s, the dose rate indications, so far, have had to be reduced in small steps over a period of about 35 years by nearly a factor of 2. As regards the (106)Ru ophthalmic plaques, the NIST 2001 calibration has resulted in a comparable reduction of the dose rate indications of up to a factor of 2 within the period of about several months. Thus, in the previous history of radiotherapy this case must be regarded as unique, because for the first time ever, an urgently needed recalibration has been protracted for such an unduly long period of time.

Calibration↗

PubMed2004

Postmastectomy radiotherapy of the chest wall. Comparison of electron-rotation technique and common tangential photon fields.

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.

Abdomen↗

PubMed2004

Palliative percutaneous radiotherapy in non-small-cell lung cancer.

Percutaneous radiotherapy is an effective tool for the palliative treatment of patients with non-small-cell lung cancer (NSCLC). About two thirds of patients experience a notably improvement of symptoms after palliative radiotherapy. A whole variety of very different radiation schedules like a single fraction of 10 Gy, 2 fractions of 8.5 Gy, 10 fractions of 3 Gy, 25 fractions of 2 Gy, and others have been used for palliation. The effects of these different schedules have been compared in a total of 11 randomized trials of which 10 reported survival data and form subject of this review. According to these studies, an increase in total irradiation dose does not substantially prolong median survival, but results in a significant better 1-year survival. A comprehensive review of the data reveals that patients with poor performance status (ECOG score > or = 3) do not benefit from higher doses, but patients with good performance status do benefit. Patients with poor performance status, and patients with large distant tumour burden regardless of their performance status, are efficiently treated by a short course of relatively low dose radiotherapy. Schedules like 2 x 8.5 Gy and 4 x 5 Gy are most appropriate in this situation. For patients with good performance status the choice of the optimal radiation schedule is less clear. Schedules with total doses between 30 and 45 Gy in 2.5-3.0 Gy fractions should be preferred in these situations.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Experimental thermoradiotherapy in malignant hepatocellular carcinoma.

PURPOSE: The human liver is known to be a relatively radiosensitive organ that develops clinically relevant late radiation hepatitis subsequent to whole liver treatment with total doses above 30 Gy in conventional fractionation. Experimental data, as well as clinical series, have demonstrated that hyperthermia of solid tumors in addition to radiotherapy enhances tumor growth inhibition and tumor control probability. We therefore developed an experimental model for combined radiotherapy and hyperthermia of the liver in transplantable rat Morris hepatoma 3924A. METHODS AND MATERIALS: A cube of approximately 8 mm(3) was implanted subcapsularly into the middle liver lobe of 59 male syngenic ACI rats weighing approximately 180-200 g. On Day 16 after tumor implantation, irradiation of the tumor-bearing liver with either 0 Gy/25 Gy/35 Gy/45 Gy total dose in 10 fractions +/- hyperthermia (target temperature 40-42 degrees C) twice a week was initiated. Energy deposition was monitored by temperature probes in the liver and esophagus of the rats. Determination of tumor volume with magnetic resonance imaging was performed 2 to 5 weeks after the end of therapy. The tumor growth rates could be estimated for 44 rats. If the growth rate was positive (37 rats), the inverse of the growth rate was interpreted as the time to 10-fold tumor volume. Otherwise the maximum observation time was considered as a censored value in a parametric survival analysis. RESULTS: Intrahepatic temperature probes showed a temperature plateau of greater than 40 degrees C after 5 to 8 min subsequent to initiation of hyperthermia. The target temperatures could be maintained for at least 22 min > or =40 degrees C and 10 min > or =41 degrees C, respectively. Median plateau temperature in liver, esophagus, and epicutaneously was 41.2 degrees C (standard deviation [SD] 0.7 degrees C; range 38.2 to 43.3 degrees C), 40.4 degrees C (SD 1.08 degrees C; range 38.9 to 41.8 degrees C), and 40.8 degrees C (SD 0.8 degrees C; range 38.2 to 42.7 degrees C), respectively. Elevation of the temperature in the esophagus correlated with intrahepatic temperatures in the range of 39-42 degrees C, r = 0.957. The increase in time to 10-fold tumor volume for each step of irradiation dosage was by 34% (95% confidence interval [CI] 20% to 49%) without hyperthermia and by 60% (95% CI 47% to 80%) with hyperthermia (p < 0.0001). CONCLUSION: Treatment outcome after experimental percutaneous thermoradiotherapy in intrahepatically implanted Morris hepatoma 3924A was related to total dose of irradiation and concurrently administered regional hyperthermia. An increased radiosensitivity due to hyperthermia (<42 degrees C) has to be assumed.

Animals↗

PubMed2003

The tyrosine kinase Lck is involved in regulation of mitochondrial apoptosis pathways.

The induction of apoptosis requires the activation of a highly coordinated signaling network ultimately leading to the activation of caspases. In previous experiments we and others have shown that the tyrosine kinase Lck is required for adequate apoptosis induction in response to ionizing radiation, ceramide incubation and overexpression of the HIV-TAT protein. However, the position of Lck within given apoptotic signaling cascades remains unclear. We therefore aimed to define the role of Lck during radiation-induced apoptosis. Apoptosis induction in response to ionizing radiation, CD95 or TRAIL receptor stimulation was determined in Jurkat T-cells, the Lck-deficient Jurkat clone JCaM1.6- and Lck-retransfected JCaM1.6/Lck. No apoptosis, release of cytochrome c, breakdown of the mitochondrial potential were detectable during the first 48 h after irradiation of JCaM1.6 cells. In parallel, no activation of caspase-9, -8 and -3 was detectable. Since mitochondrial apoptosis pathways act within a feedback mechanism during death-receptor-mediated apoptosis, the influence of the Lck defect on CD95/Fas/Apo-1-L or TRAIL-induced apoptosis was also tested. Both stimuli induced apoptosis in Lck-deficient cells. However, the kinetics of apoptosis induction determined by caspase-8, -9 and -3 activation as well as deltapsi(m) breakdown was slowed. We conclude that the Lck deficiency influences early steps during radiation-induced mitochondrial alterations.

Apoptosis↗

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

[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

Molecular requirements for the combined effects of TRAIL and ionising radiation.

BACKGROUND AND PURPOSE: Previously it was shown that combination of death ligand TRAIL and irradiation strongly increases cell kill in several human tumour cell lines. Since Bcl-2 overexpression did not strongly interfere with the efficacy, components of the mitochondrial death pathway are not required for an effective combined treatment. In the present study the minimal molecular prerequisites for the efficacy of a combined treatment were determined. MATERIALS AND METHODS: Apoptosis induction in control, caspase-8 and FADD negative Jurkat cells, BJAB control and FADD-DN cells was analysed by FACS. Activation of caspase-8, -10 and -3 and cleavage of PARP was determined by immunoblotting. TRAIL receptors were activated using recombinant human TRAIL. Surface expression of TRAIL receptors DR4 and DR5 was analysed by FACS. RESULTS: Jurkat T-cells express the agonistic DR5 receptor but not DR4. Presence of FADD was found to be essential for TRAIL induced apoptosis. Caspase-8 negative cells show very low rates of apoptosis after prolonged stimulation with TRAIL. No combined effects of TRAIL with irradiation could be found in FADD-DN overexpressing and FADD deficient cells. However, the combination of TRAIL and irradiation clearly lead to a combined effect in caspase-8 negative Jurkat cells, albeit with reduced death rates. In these cells activation of the alternative initiator caspase-10 could be detected after combined treatment. CONCLUSION: Our data show that a combined therapy with TRAIL and irradiation will only be effective in cells expressing at least one agonistic TRAIL receptor, FADD and caspase-8 or caspase-10.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Antiangiogenesis and radiotherapy: what is the role of combined modality treatment?

The formation of new blood vessels is a prerequisite for the growth of primary and metastatic tumour. Thus, strategies that aim at the inhibition of tumour angiogenesis have gained considerable interest in recent years. Furthermore, there is a need to identify the role of antiangiogenic agents in conjunction with conventional anticancer modalities like chemotherapy or radiotherapy. It is the objective of this review to summarise experimental data for different antiangiogenic agents used for combined modality experiments with radiotherapy. Promising data have been reported for a series of antiangiogenic agents for combined modality treatment with radiotherapy using tumour growth delay as the primary end-point. Yet, the results from different agents with various tumour lines are contradictory in part. Furthermore, enhancement of local tumour control, the main objective of curative radiotherapy, has so far been demonstrated for only two agents (DC101 and CA4DP), while experiments using TNP-470 even revealed a reduction of local tumour control when combined with irradiation. Finally, detailed studies investigating the modulation of normal tissue reactions for the combination of radiotherapy and inhibitors of angiogenesis are pending so far. Thus, experimental data currently available do not consistently support the beneficial effects of combined modality treatment with inhibitors of angiogenesis and radiotherapy. We therefore conclude that there is still a long way to go until we know which antiangiogenic agent will clinically be suitable for what tumour entity for combined treatment of radiotherapy and inhibitors of angiogenesis.

Angiogenesis Inhibitors↗

PubMed2002

Reimplantation of extracorporeal irradiated bone segments in musculoskeletal tumor surgery: clinical experience in eight patients and review of the literature.

BACKGROUND: Two methods are available for extracorporeally devitalizing resected tumor-bearing bone specimens, the simpler of which, autoclaving, has substantial disadvantages. We present our experience with the alternative reconstruction technique of reimplantating extracorporeally irradiated specimens (IEIR) PATIENTS AND METHODS: Eight patients who had primary malignant bone tumors of the long bones were managed with wide en bloc resection and IEIR. The segments were fixed by either plate osteosynthesis, knee arthrodesis rod, or intramedullary nailing. All seven patients with high-grade tumors received chemotherapy. RESULTS: After a median follow-up of 66 months (40-76) five of eight patients were continuously free of disease. One man with a chondroblastic osteosarcoma developed pulmonary metastases which were resected. One woman with teleangiectatic osteosarcoma developed a local recurrence in the soft tissue without contact to the irradiated reimplant. At the latest follow-up, 58 months after resection of the pulmonary metastases and 28 months after resection of the locally recurrent tumor, there was no evidence of disease in either patient. Another woman 67 months after IEIR for an osteosarcoma of the distal femur developed a subcutaneous metastasis of the scalp and the thoracic wall and an ossifying pulmonary metastasis. At the time of writing she is receiving chemotherapy. After a median duration of 4.3 months (2.3-25.2) all graft-host junctions had healed. The functional result was good in four patients and excellent in the other four. CONCLUSIONS: Limb salvage using reimplantation of extracorporeally irradiated tumor-bearing bone segments for reconstruction offers an excellent reconstruction method in appropriately selected patients compared with other options of management.

Adolescent↗

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

Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma.

The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDu(dd)) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11 x 4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0-57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17-43) days, fractionated irradiation in 31 (25-35) days and combined Mitomycin C plus fractionated irradiation in 65 (58-73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95-1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13-1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model.

Animals↗

PubMed2002

Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder?

OBJECTIVES: This study evaluated for the first time in intraindividual comparison the conception of care with creme or powder. Acute skin reactions on the left and right side of the neck during symmetrically performed radiotherapy and subjective impairment were assessed. PATIENTS AND METHODS: Twelve patients receiving radiotherapy of the head-and-neck region up to 50, 60, 66 and 72 Gy, respectively, were asked to treat one side of the neck with creme, the contralateral side with powder after random assignment. Objective and subjective assessment and photodocumentation were performed at therapy onset and weekly during therapy. The photodocumentation provides an impressive course of acute skin reactions under these care concepts. RESULTS: Altogether we saw no relevant difference in favor of care with creme or powder according to objective as well as subjective assessment criteria (Figure 2 and 3). In this intraindividual comparison the results are independent from interindividual different sensitivity to radiotherapy, total dose or fractionation. Therefore the small patient number is a minor limitation for evidence. Our results are in accordance to trials comparing other care concepts. CONCLUSIONS: A relevant effect concerning onset and degree of acute skin reactions or differences in symptom relief could not be demonstrated. Both conceptions are to be regarded equal in terms of subjective symptom relief and in extent of acute skin reactions. The lack of differences may be explained by the fact that the underlying pathophysiological processes cannot be influenced by topical agents.

Adult↗

PubMed2002

Selective lymph node dissection following hyperfractionated accelerated radio-(chemo-)therapy for advanced head and neck cancer.

BACKGROUND: 2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed. PATIENTS AND METHODS: Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV MO head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection. RESULTS: After a median follow-up of 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients. CONCLUSIONS: Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer.

Adult↗

PubMed2002

Postmastectomy electron-beam-rotation irradiation in locally advanced breast cancer prognostic factors of locoregional tumor control.

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.

Breast Neoplasms↗

PubMed2002

Differential expression of inflammatory mediators in radiation-impaired wound healing.

BACKGROUND: Radiation impairs healing, although the underlying mechanisms are not clearly defined. Normal healing requires a fine balance of promoting and inhibiting factors. We hypothesize that there may be a down-regulation of promoting factors (nitric oxide) and, in turn, an up-regulation of healing inhibiting factors (TNF-alpha and IFN-gamma) in the wound after radiation. MATERIAL AND METHODS: Groups of 10 rats were irradiated using single dose 12 or 24 Gy electron radiation at the dorsal skin. Control rats were sham-irradiated. On Day 5 a skin incision in the irradiated area was performed and polyvinyl alcohol sponges were inserted subcutaneously. Rats were sacrificed 10 days later to determine the wound-breaking strength and reparative collagen deposition. Nitrite and nitrate (index of NO synthesis), TNF-alpha, and IFN-gamma were measured within the wound fluid. Expression of the inducible NO-synthase (iNOS) was investigated by immunohistochemistry. Wound-derived fibroblasts were tested in vitro for NO and collagen synthesis. RESULTS: Irradiation significantly reduced wound collagen deposition and wound-breaking strength (P < 0.05). Impaired healing was reflected in diminished wound NO synthesis and iNOS expression (P < 0.01). TNF-alpha and IFN-gamma were increased in irradiated wounds (P < 0.05). Ex vivo, NO synthesis and collagen deposition by fibroblasts from irradiated rats were decreased (P < 0.01). In vitro irradiation of fibroblasts from nonirradiated rats decreased both NO and collagen production (P < 0.01). CONCLUSION: Radiation-impaired healing is reflected in an imbalance of promoting and inhibiting factors, leading to increased levels of TNF-alpha and IFN-gamma and decreased NO expression in the wound.

Animals↗