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M J Eble

Publications and source records attributed to M J Eble.

At least 19 recordsLinked to original sources
PubMed2003

[Sonografic evaluation of oxygenation in head and neck cancer].

BACKGROUND: Tumor oxygenation is an important aspect of radiosensitivity. The authors describe a new method for a non-invasive assessment of tumor oxygenation in head and neck cancer. PATIENTS AND METHODS: A group of 20 patients with neck metastases of squamous cell cancer of the head and neck region was surveyed. At first a pO (2)-polarography was performed in the metastatic cervical nodes to investigate the tissue oxygenation. In a second step, the vascularisation of these nodes was visualised by color duplex sonography. In order to evaluate the extent of vascularisation in these nodes, the density of color pixels was quantified by a custom-made software program. The color pixel density and the pO (2) values were correlated and the statistic significance was calculated by Pearson's test. RESULTS: The mean vascularisation as evaluated by the means of color duplex sonography was 7.78 % [95 % CI 6.04 - 9.51]. The interindividual pO (2) values in the stroma of metastatic lymph nodes ranged between 9.0 and 27.4 mmHg (16.6 [95 % CI 14.06 - 19.13]). The mean values of pO (2)-fractions < 2.5/< 5.0/10 mm Hg were 32.25 %, 44.25 % and 53.29 % respectively. The median value of the pO (2)-fraction was 10.49 % [95 % CI 7.13 - 13.85]. The vascularisation as evaluated by color pixel density showed a statistically significant correlation with the pO (2)-fractions < 5.0 and < 10 mmHg (p < 0.045 and < 0.0001) and with the mean (p < 0.002) and median values of tissue pO (2) values (p < 0.0001) in polarography. CONCLUSION: The results in a limited number of patients suggest, that the proposed sonographic method allows a reliable non-invasive evaluation of tissue oxygenation in cervical metastases of squamous cell head and neck cancers.

Adult↗
PubMed2002

IORT (intraoperative radiotherapy) in neuroblastoma: experience and first results.

Intraoperative radiotherapy (IORT) permits the application of a single large radiation dose to a malignant mass at the time of surgery sparing adjacent normal tissue from irradiation. Since 1996 we have used IORT to treat 13 children with neuroblastoma, stage 3 - 4. In all cases the tumour was not radically resectable at the first operation. Ultrasound, CT and MRI were performed and patients were treated with chemotherapy according to the NB90 protocol. The second-look operation was performed in the IORT operating room where the tumour was resected as completely as possible, while keeping the "no risk" principle in mind. Localised radiation of the residual tumour was 8 - 10 Gy. The child was monitored via 3 video cameras. No technical problems occurred during IORT application. The follow-up time was 6 - 69 months (May 2001). One patient died due to tumour progression, another in complete remission died after 9 months due to sepsis. The clinical course of 2 patients was complicated by a renal artery stenosis and a mesenteric artery occlusion. All other patients are in complete remission with regular follow-up examinations. Although the results are promising the number of patients is too small as yet for statistical analysis. However, IORT can be safely applied in patients with high-risk neuroblastomas, reducing the dose, side effects and resulting in remission.

Abdominal Neoplasms↗
PubMed2002

Interstitial brachytherapy with permanent seed implants in early prostate cancer.

Excellent clinical results after permanent seed implantation have been reported by various centers in large cohorts of patients. However, all of these had extensive experience in this special field of radiotherapy and the therepy and the follow-up time is too short for definite conclusions. The fact that this option of treatment can be carried out on an outpatient basis and that it allows to get the patient back to normal as far as social environment and work are concerned, has led to wide acceptance of this particular mode of therapy. Therefore, permanent seed implantation is a possible treatment option for localized prostate cancer and can be offered to patients with T1- T2a tumors, PSA levels of < 10 and a Gleason score of < 7. By using permanent seed implantation in these selected patients, it seems possible to achieve results comparable with surgery alone or percutaneous, 3D-planned radiotherapy.

Adenocarcinoma↗
PubMed2001

Correlation of intraoperatively irradiated volume and fibrosis in patients with soft-tissue sarcoma of the extremities.

PURPOSE: To investigate the influence of intraoperatively irradiated volume on soft-tissue fibrosis. METHODS AND MATERIALS: Fifty-three patients with soft-tissue sarcoma of the extremities were treated with intraoperative radiotherapy (IORT) (median dose 15 Gy) and postoperative fractionated therapy (median dose 46 Gy). The median follow-up was 41.5 months (range 18-94). Late toxicity was classified according to the LENT-SOMA criteria. A Cox regression model was calculated to identify the parameters that could influence soft-tissue fibrosis Grade 3 or 4. Five parameters were observed: extent of surgical procedure, IORT in case of recurrence, extent of IORT volume, extent of IORT dose, and extent of postoperative volume. In addition, a logistic regression model was calculated to demonstrate the relationship between the IORT volume and fibrosis development. RESULTS: The overall survival rate after 5 years was 84%. The actuarial tumor control rate was 90% after 5 years. Eleven patients developed soft-tissue fibrosis. Five patients developed Grade 3 fibrosis and 1 patient developed Grade 4 fibrosis. Only the IORT volume had a significant influence on Grade 3 or 4 fibrosis development. An IORT volume of 210 cm(3) conveyed a 5% risk (confidence interval 1-20%) of the development of severe fibrosis. The risk of severe Grade 3 or 4 fibrosis increased to 50% (confidence interval 15-80%) if a volume of 420 cm(3) was irradiated. CONCLUSION: The effect of volume in patients treated with IORT was remarkable. The ratio of side effects was relatively low. The risk of soft-tissue Grade 3 or 4 fibrosis increased with the extent of the IORT volume. Compared with the literature, IORT provides excellent local control in these patients.

Adolescent↗
PubMed2000

Repeatability and prognostic impact of the pretreatment pO(2) histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this study was to evaluate the repeatability and the predictive relevance of the pretreatment pO(2) histography on the survival of patients with advanced head and neck cancer. PATIENTS AND METHODS: From July 1995 to August 1998, polarographic pO(2) measurements of lymph node metastases before therapy were performed in altogether 60 patients with histologically proven squamous cell carcinoma of the head and neck using the Eppendorf histograph. Forty-one of 60 patients were treated with an accelerated-hyperfractionated radiotherapy regimen with or without simultaneous chemotherapy as part of a multicenter phase III study. In 23 of 60 patients, two repeated independent measurements of the same tumor were performed with a time interval of approximately 24 h between the two measurements. RESULTS: The multivariate analysis revealed the fraction of pO(2) values </=2.5 mmHg as the only significant prognostic factor for the survival (P=0.05) in the 41 study patients. No correlation was found between tumour oxygenation and the volume of the measured lymph node metastases or the haemoglobin concentration. The coefficient of variation of the repeated measurements representing the assay variability was 57-68% of the total variation. CONCLUSION: Our data support the concept of the relevance of the pretreatment tumour hypoxia for the prognosis of patients with head and neck cancer after fractionated radiotherapy. Because of the relative poor repeatability of the pO(2) histography and the small patient number, further studies are required to confirm this finding and to evaluate the most relevant oxygenation parameter for clinical endpoints.

Adult↗
PubMed2000

Oxygenation of advanced head and neck cancer: prognostic marker for the response to primary radiochemotherapy.

Recent clinical studies suggest that the degree of tumor oxygenation may be predictive of the response of radiation therapy for cancer. In an exploratory investigation of cervical lymph node metastases in 27 patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx, this relationship was investigated by means of oxygen measurements with an Eppendorf PO (2) histograph. The measurements were made before the start of radiation therapy and after the first week of therapy. Clinical response was evaluated 6 weeks after the completion of therapy. Before therapy, marked hypoxia was observed in the lymph node metastases, with a mean PO (2) value of 16.1 +/- 8.2 mm Hg and a hypoxic fraction (PO (2) < 10 mm Hg) of 56.4% +/- 20.0%. After the first week of radiation (9 Gy) there was a general reoxygenation (DeltaPO (2) = 5.0 +/- 10.1 mm Hg, P < 0.05; Deltahypoxic fraction = -11.3% +/- 31.3%, P = 0.11). A relationship between the degree of reoxygenation and tumor response was not observed. Patients without at least partial lymph node response (n = 8) showed poorer pretherapeutic oxygenation (PO (2) mean = 11.1 +/- 2.9 mm Hg) than those who responded to the therapy (n = 19, PO (2) mean = 18.2 +/- 8.8 mm Hg). In this investigation of a defined set of patients with advanced carcinoma of the oropharynx and hypopharynx, we found that pretherapeutic oxygenation data are predictive for the therapeutic response to radiation therapy or radiochemotherapy.

Adult↗
PubMed2000

Measurement of hypoxia using the comet assay correlates with preirradiation microelectrode pO2 histography in R3327-AT rodent tumors.

Polarographic determination of tumor oxygenation by Eppendorf histography is currently under investigation as a possible predictor of radiotherapy outcome. Alternatively, the alkaline comet assay has been proposed as a radiobiological approach for the detection of hypoxia in clinical tumor samples. Direct comparisons of these methods are scarce. One earlier study with different murine tumors could not establish a correlation, whereas a weak correlation was reported for a variety of human tumors. Considering the different end points and spatial resolution of the two methods, a direct comparison for a single tumor entity appeared desirable. Anaplastic R3327-AT Dunning prostate tumors were grown on Copenhagen rats to volumes of 1-6 cm(3). Eppendorf histography (100-200 readings in 5 parallel tracks) for 8 different tumors revealed various degrees of oxygenation, with median pO(2) values ranging from 1.1 to 23 mmHg. Within 5 min after an acute exposure to 8 Gy (60)Co gamma rays, tumors were excised from killed animals and rapidly cooled to limit repair, and a single cell suspension was prepared for use with the comet assay. The resulting comet moment distributions did not exhibit two subpopulations (one hypoxic and the other aerobic), and a hypoxic fraction could not be calculated. Instead, the average comet moment distribution was taken as a parameter of overall strand break induction. Corresponding experiments with tumor cells grown in vitro allowed us to derive the relationship between the oxygen enhancement ratio (OER) for the average comet moment and oxygen partial pressure (Howard-Flanders and Alper formula). The validity of this relationship was inferred for cells exposed in situ, and the convolution of a pO(2) distribution with the formula of Howard-Flanders and Alper yielded an array of expected OER values for each tumor. The average expected OER correlated well with the average comet moment (r = 0.89, P < 0.01), and the in situ comet moment distributions could be predicted from the Eppendorf data when 50% repair was taken into account, assuming a 5-min damage half-life. The findings confirm the potential of interstitial polarography to reflect radiobiologically relevant intracellular oxygenation, but also underscore the confounding influence of differences in repair that may occur when cells are prepared from irradiated tissues for use with the comet assay.

Adenocarcinoma↗
PubMed1999

Rise of oxygenation in cervical lymph node metastasis during the initial course of radiochemotherapy.

It has been hypothesized that during radiation treatment a reoxygenation of hypoxic tumor tissue takes place. To test this hypothesis, we have investigated whether reoxygenation in lymph node metastases could be determined by invasive PO (2) measurements. Through a hypodermic needle inserted transcutaneously into tumor-positive lymph nodes, polarographic oxygen determinations were made in 18 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx. These measurements were performed before therapy and a week after the onset of radiotherapy or radiochemotherapy, respectively. Low PO (2) values before treatment (mean value of the patient's median was 12.6 mm Hg PO (2)) and a mean hypoxic fraction (PO (2) < 5 mm Hg) of 39.6% indicated manifest tumor hypoxia. After 1 week of treatment, a significant increase in the median PO (2) (mean value of shift: 7.3 mm Hg) and a reduction in the hypoxic fraction (mean value of shift: 13.4% PO (2) < 5 mm Hg, P < 0.03) were observed after both radiotherapy and radiochemotherapy. Thus invasive PO (2) histography fulfills the requirements for a method to confirm tumor hypoxia in head and neck tumors. The results obtained indicate that reoxygenation occurs during the initial phases of radiotherapy and radiochemotherapy, and they will form the basis for future comparative investigations on the possible influence of hypoxic parameters on tumor responsiveness toward radiation and radiochemotherapy.

Adult↗
PubMed1998

Intraoperative radiotherapy as adjuvant treatment for stage II/III rectal carcinoma.

In recent years, many efforts have focused on combined radiotherapy and chemotherapy as adjuvants to curative surgery in patients with stage II and III (UICC) rectal carcinomas. Intraoperative radiotherapy (IORT) makes it possible to increase the total irradiation dose in a locally restricted area while sparing normal mobile organs, but it is limited by increased late toxicity. A prospective phase I/II study was designed to evaluate the efficacy of moderate-dose intraoperative and external beam radiotherapy (IO-EBRT), in some cases with concomitant chemotherapy. Sixty-three patients with a stage II or III rectal carcinoma were eligible for analysis (median follow-up 30.6 months). Fifty-four patients had undergone a complete resection (RO). Mean IORT dose was 11.3 Gy and mean EBRT dose 41.4 Gy. In 45 patients (71.4%) concomitant chemotherapy was delivered (5-FU, leucovorin). Two patients suffered local failure. However, overall local tumor control was markedly improved compared to historical controls (96.8% vs 66.2%). Patients treated with IO-EBRT showed a reduced incidence of distant metastases after concomitant chemotherapy (17.6% vs 38.8%). A 4-year actuarial relapse-free survival of 82% was obtained after IO-EBRT plus chemotherapy, and 59% after IO-EBRT alone. The postoperative course was unremarkable in 47.6% of patients. No radiation colitis or neuropathy occurred. Moderate-dose IORT and EBRT is safe, taking into account related late toxicities. It is an effective local treatment approach, resulting in an encouraging local control rate.

Combined Modality Therapy↗
PubMed1998

[The intraoperative radiotherapy (IORT) of locally spread and recurrent renal-cell carcinomas].

PURPOSE: Renal cell carcinomas are relatively radioresistant. After macroscopically incomplete tumor resection conventional external beam radiotherapy is dose-limited and additional systemic treatment with chemotherapy ineffective to achieve local control. In a pilot study the role of intraoperative radiotherapy in the treatment of locally advanced or recurrent renal cell carcinomas was analysed. PATIENTS AND METHODS: From January 1992 to July 1994 11 patients with a primary (n = 3) or recurrent renal cell carcinoma had IORT. One patient had complete resection and in 3 respectively 7 patients microscopically or macroscopically residual disease was left. Using 6 to 10 MeV, a single dose of 15 to 20 Gy was delivered to the fossa renalis and the corresponding paraaortic area. Based on three-dimensional treatment planning, additional external beam radiotherapy was given 3 to 4 weeks later (40 Gy, 2 Gy SD, 23 MV). RESULTS: After a mean follow-up of 24.3 months 5 patients had died of distant metastases (lung, liver, bone, mediastinum) with a mean survival time of 11.5 months. Mean disease-free interval was 6.4 months. One patient suffered from a second malignancy. Two patients are alive with distant metastases. Local tumor control in the entire group was 100%. The calculated 4-year overall and disease-free survival was 47% and 34%. The postoperative course was affected in 3 patients (abscess n = 1, short dehiscence of the abdominal wound n = 2). The gastrointestinal toxicity during external beam radiotherapy was low. No IORT-specific late adverse effects were observed. CONCLUSION: After incomplete tumor resection local tumor control with minimal therapy related side effects could be achieved using intraoperative radiotherapy. With IORT the dose limitation in the radiotherapy of renal cell carcinoma could be overcome. The high distant metastases rate relativized overall prognosis. The low morbidity rate justifies further evaluation of this technique.

Carcinoma, Renal Cell↗
PubMed1998

[Topical radiotherapy in the management of skeletal metastases].

Local radiotherapy plays an important role in the palliative management of bone metastases. Different concepts of dose fractionation are in use. A judgement of the efficacy of these concepts should be based on their different palliative treatment endopoints. The efficacy of radiotherapy using published data can be analysed with respect to pain relief and re-establishment of bone integrity as treatment endopoints. Trials stratifying radiooncological techniques according to an optimization of quality of life are missing. Nevertheless, the rationale for individual treatment in daily work is based on systemic tumor extent, life expectancy, the kind of symptoms and the location of the metastasis in question. In patients with reduced live expectancy a remarkably high chance of pain relief (70%) could be achieved with single doses of 8 Gy. The latency period until pain relief is shorter with higher single doses. In case of recurrence of pain reirradiation with a single dose results in an equally high response rate. Patients with a solitary metastasis, patients with longer live expectancy and patients with pathological fractures should be treated with 'curative' doses, aimed to cause maximum tumor cell killing. Impaired bone stability in patients who are not suitable for surgical intervention requires orthetic supply. Apart from the effect of pain relief, remineralization is the important treatment goal for these patients. Conventional radiotherapy with doses of 40-50 Gy resulted in remineralization in 60-80% of the patients 4-8 weeks after irradiation. Remineralization could not be acceierated by short course fractionation courses.

Bone Neoplasms↗
PubMed1998

Moderate dose intraoperative and external beam radiotherapy for locally recurrent rectal carcinoma.

BACKGROUND AND PURPOSE: Late adverse effects (i.e. neuropathy, chronic bowel obstruction) limit the effective dose given in intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). Initial results of a multi-modality treatment approach using moderate dose IORT and moderate dose EBRT are presented. PATIENTS AND METHODS: Thirty-one consecutive patients with recurrent rectal carcinomas had IORT and EBRT after complete (R0, n = 14) or incomplete resection (R1, n = 9; R2, n = 8). The mean [ORT dose was 13.7 Gy (range 12-20 Gy) supplemented with an EBRT dose of 41.4 Gy. Twenty-two patients had preoperative EBRT and 22 patients had concomitant chemotherapy (5-FU, Leucovorine). RESULTS: After a median follow-up of 28 months, 16 patients had re-recurrent disease and 11 patients had died. Nine patients failed locally (four in-field, four marginal and one anastomotic re-recurrence), three combined with distant metastasis, resulting in overall and IORT infield local control rates of 71% and 87%, respectively. Distant metastases alone were found in seven patients. The 4-year overall and relapse-free survival rates were 58% and 48%, respectively. After incomplete resection the local failure rate increased (R0 21%, R1/2 35%) and the 4-year relapse-free survival rate decreased significantly (29% versus 71%) due to a markedly increased distant metastasis rate (53% versus 7%). Acute and late toxicities were not increased. CONCLUSION: The combination of moderate dose IORT and EBRT is a safe and efficacious component in a multi-modality treatment approach.

Antineoplastic Agents↗
PubMed1997

[Polarographic detection of reoxygenation of lymph node metastases in the initial phase of primary radio- and radiochemotherapy in patients with advanced squamous epithelial carcinomas of the head and neck].

The therapeutic effect of radiotherapy depends amongst other things on the degree of oxygenation of tumour tissue. Epithelial carcinomas of the head-neck region exhibit considerable hypoxic areas which vary markedly between individuals and not encompassed by current staging and grading. It is assumed that during radiation treatment a reoxygenation of hypoxic tumour cells takes place. It was investigated wether the occurrence of reoxygenation could be determined by invasive oxygen partial pressure measurements in lymph node metastases. Using a needle probe inserted transcutaneously into a lymph node polarographic oxygen determinations (Eppendorf pO2-Histiograph) were made on 13 patients with advanced oro- and hypopharyngeal carcinomas before therapy and after a week of accelerated radio- or radiochemotherapy. Low pO2 values before treatment (median 13.5 mmHg, average 20.3 mmHg) and a hypoxic fraction (pO2 < 10 mmHg) of 45.2% indicated manifest tumour hypoxia. After the first week of treatment a significant increase in the median- (24.1 mmHg) and the average pO2 (28.2 mmHg) as well as a reduction in the hypoxic fraction (27%) were observed. Invasive pO2 histiography fulfils the requirements for a method to confirm tumour hypoxia in head-neck tumours. The results obtained indicate that reoxygenation occurs during the initial phases of radio- and radio-chemotherapy.

Adult↗