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K Haustermans

Publications and source records attributed to K Haustermans.

At least 19 recordsLinked to original sources
PubMed2007

Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

Adult↗
PubMed2005

Chemo-radiotherapy versus radiotherapy alone in the pre-operative treatment of resectable rectal cancer.

AIM: To determine the differences in downstaging, local control (LC), disease free survival (DFS) and overall survival (OS) between combined pre-operative chemoradiation and pre-operative radiotherapy alone in the treatment of resectable rectal cancer. METHODS: One hundred and ten patients who underwent pre-operative radiotherapy or chemo-radiotherapy were reviewed. Fifty-seven patients were treated with radiotherapy (30 Gy/3 Gy) alone and 53 patients with chemo-radiotherapy (bolus 5FU+45 Gy/1.8 Gy). The median interval between the end of neo-adjuvant treatment and surgery was 28 and 46 days for the patients treated with radiotherapy alone and chemo-radiotherapy. RESULTS: The groups were homogeneously distributed for all characteristics except for cN-stage with more clinically node positive patients in the combined modality treatment group (47 vs 73%). A significant downstaging for tumour and/or lymph node status was observed in both groups. More ypT0-x-is were observed after chemoradiation than after radiotherapy alone (26 vs 7%; p=0.02). The local control rate at 3 years was 94% for both groups. DFS after radiation and chemoradiation was comparable with a 3-year DFS of 83 and 88%, respectively. CONCLUSION: Both pre-operative schemes have similar outcomes concerning DFS, OS and LC. Tumour downstaging is associated with improved survival.

Adenocarcinoma↗
PubMed2004

Efficacy and tolerability of radiotherapy as treatment for bicalutamide-induced gynaecomastia and breast pain in prostate cancer.

OBJECTIVE: To assess the efficacy and tolerability of localised radiotherapy for the treatment of bicalutamide ('Casodex''Casodex' is a trademark of the AstraZeneca group of companies.)-induced gynaecomastia and/or breast pain. METHODS: This open-label, non-comparative, multicentre study included 51 patients receiving bicalutamide 150 mg for the treatment of non-metastatic prostate cancer (T1b-T4, Nx, M0). Patients who developed symptomatic gynaecomastia and/or breast pain received two 6-Gy fractions of external-beam radiation to the breasts and were then assessed at two 3-monthly follow-up visits. RESULTS: 37/51 (72.5%) patients experienced gynaecomastia and 41/51 (80.4%) experienced breast pain, typically within the first 6 months. Twenty seven and 38 patients, respectively, went on to receive breast irradiation. Following radiotherapy, gynaecomastia improved or resolved in 7/27 (25.9%) and 2/27 (7.4%) cases, respectively, and breast pain improved or resolved in 12/38 (31.6%) and 3/38 (7.9%) cases, respectively. No change was observed in 7 patients (25.9%) with gynaecomastia and 12 patients (31.6%) with breast pain, while 9 patients (33.3%) and 8 patients (21.1%), respectively, worsened. Radiotherapy-related adverse events, reported by 18/41 (43.9%) patients, were generally mild and short lived (median duration approximately 5 weeks). CONCLUSIONS: Therapeutic radiotherapy, using two fractions of 6 Gy external-beam radiation to the male breast, improves the intensity of bicalutamide-induced gynaecomastia and/or breast pain in approximately one-third of patients. Adverse events were often mild and short lived.

Adenocarcinoma↗
PubMed2004

Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry.

This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P<0.05) was obtained between the hypoxic volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO-stained tumour sections (r=0.9066; P=0.0001), regardless of the selected threshold between 1.4 and 2.2. A similar observation was made with the CA IX staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas indicates the value of the noninvasive imaging method to measure hypoxia in whole tumours.

Animals↗
PubMed2004

Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer.

Positron emission tomography (PET) using the positron emitting glucose analogue 18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore, there is a growing need for a clear definition of the relative position of PET within the currently available diagnostic modalities. Significant scientific data indicate that FDG-PET adds clinically useful information to the information obtained by standard means (mainly CT and endoscopic ultrasound) throughout the different phases of clinical patient management: 1) at initial diagnosis: PET detects more frequently distant lymph node involvement and organ metastases compared to conventional diagnostics, allowing a more accurate selection of the most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET allows early identification of non-responding patients. Indeed, the metabolic response as measured by serial FDG-PET can be used to predict the clinical and histopathological response. Moreover, the PET-response seems to be related to overall and disease free survival; 3) after a treatment: FDG-PET allows accurate assessment of the residual tumor load; 4) in the follow up: FDG-PET allows accurate detection and restaging of recurrent disease.

Esophageal Neoplasms↗
PubMed2002

Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer.

AIMS: This prospective study was designed to determine the utility of 18F-labelled deoxyglucose (FDG) in positron emission tomography (PET) (FDG-PET) for assessing the response to neoadjuvant chemoradiation therapy (CRT) in locally advanced oesophageal tumours. PATIENTS AND METHODS: Thirty-six patients with locally advanced oesophageal cancer (clinical T4 stage) without organ metastases, underwent FDG-PET before and 1 month after CRT. Patients were classified as major responders by serial FDG-PET when the post-CRT PET demonstrated a strong reduction of FDG uptake at the primary tumour site (>80% reduction of tumour-to-liver uptake ratio) without any abnormal FDG uptake elsewhere in the body. PET response was compared with histology obtained during post-induction transthoracic oesophagectomy. RESULTS: A strong correlation was found between the extent of lymph node (LN) involvement as shown by the pre-CRT PET and the major response rate (P = 0.001): such response occurred in nine of 11 N0M0 patients (82%), in three of nine N(1-2)M0 patients (33%) and in two of 16 patients (13%) with distant lymphatic spread. Such a correlation was not found for computed tomography or endoscopic ultrasonography. The sensitivity of serial FDG-PET for a major CRT response was 10 of 14 (71%), its specificity 18 of 22 (82%). The concordance between the response assessment by PET and histopathology was 78%. The median survival time after CRT of PET major responders compared with PET non-major responders was 16.3 months and 6.4 months, respectively. The metabolic response as measured by serial FDG-PET is a stronger prognostic factor for overall survival (P = 0.002) than the extent of LN involvement seen on the pretreatment FDG-PET (P = 0.087). CONCLUSIONS: These data indicate that CRT response as assessed by serial FDG-PET is strongly correlated with pathological response and survival.

Adenocarcinoma↗
PubMed2001

Is there a future for cell kinetic measurements using IdUrd or BdUrd?

PURPOSE: The analysis of causes of radiation failure both in retrospective series of patients with head and neck cancer and in several randomized clinical trials suggests a loss of local control as the overall treatment time increases for the same total dose. This is attributed to tumor cell proliferation during fractionated radiotherapy. As longer treatment times lead to loss of local control, it has been suggested that shorter treatment times could lead to an increase in local control. For this reason accelerated treatment regimens have been and are being designed. However, these treatments may cause severe acute reactions. Due to this, lower total doses are sometimes given. Slowly proliferating tumors, therefore, may do worse when treated with accelerated schedules compared with conventional schedules. In addition, it is not desirable to subject all patients to the more intense acute reactions of accelerated schedules. It would thus be useful to predict which tumors will rapidly proliferate during treatment and are likely to benefit from accelerated radiotherapy. The potential doubling time (Tpot) is defined as the time within which the cell population of a tumor would double if there were no cell loss. The hypothesis is that the median Tpot measured before treatment might correlate with the effective doubling time (Tp) during treatment. CONCLUSION: Tpot can be calculated knowing the labeling index (LI; proportion of cells incorporating the DNA precursor IdUrd or BdUrd) and Ts (the DNA synthesis time) measured by flow cytometry. A recent multicenter analysis has shown that the only pretreatment kinetic parameter for which some evidence is found for an association with local control is LI, not Tpot. Pitfalls associated with cell kinetic measurements such as assay variability, intratumor and intertumor variability, interlaboratory variability and the problem of an admixture of normal and malignant cells make Tpot not accurate and reproducible enough for a robust predictive assay. It therefore appears that pretreatment Tpot measurements using flow cytometry, provide only a relatively weak predictor of outcome after radiotherapy in head and neck cancer. Immunohistochemistry allows a simple measure of LI and may give additional independent information from labeling patterns, suggesting that this method is the (short term) future for clinical cell kinetic measurements using BdUrd or IdUrd.

Bromodeoxyuridine↗
PubMed2000

Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma.

PURPOSE: A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS: Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS: FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION: PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Adenocarcinoma↗
PubMed2000

Diffusion limited hypoxia estimated by vascular image analysis: comparison with pimonidazole staining in human tumors.

PURPOSE: To assess diffusion limited hypoxia in human tumors using image analysis of vasculature and to compare it with the bioreductive marker pimonidazole as an independent method. MATERIALS AND METHODS: To set up the method, nine rectal adenocarcinomas and ten squamous cell carcinomas were analyzed. To validate the method, ten squamous cell carcinomas of the cervix were analyzed from patients who were injected with pimonidazole and biopsied approximately 24 h later. Sections of the rectal and esophageal tumors were stained for vasculature, while cervix tumor sections were double stained for vasculature and pimonidazole. Tumor areas were delineated on digitized images, and the proportion of tumor tissue greater than a fixed distance from the nearest blood vessel (called diffusion limited fraction, DLF) was then calculated. The proportion of tumor area stained for pimonidazole was also measured. RESULTS: There was a wide variation between tumors in both the vascular-derived DLF and in the pimonidazole-stained fraction. Average DLFs varied between 1.5 and 92% for different tumors, with significant differences between them. The area stained by pimonidazole was significantly smaller than DLF for all tumors. The correlation between pimonidazole area and DLF was significant in three of seven tumors containing > or = 3 images. When images from all tumors (n=123) were analyzed together, the correlation was highly significant (r=0.47, P<0.0001). CONCLUSION: The vascular derived DLF correlates significantly with pimonidazole staining, but there was large scatter. Both methods may underestimate perfusion limited hypoxia.

Adenocarcinoma↗
PubMed2000

Use of thymidine analogues to indicate vascular perfusion in tumours.

Temporary reduction in blood-flow within tumour blood vessels can reduce oxygen supply leading to transient perfusion-limited hypoxia. Consequent selection of cells with mutations and reduced radiosensitivity can lead to disease progression and treatment-resistance. In the present study, we investigated whether heterogeneity of labelling after thymidine analogue administration is related to perfusion variations, and if so, could it be quantified and used as a perfusion indicator. Perfusion in murine RIF1 tumours was reduced by hydralazine or increased by nicotinamide and the mice subsequently injected with IdUrd. Tumours were halved for analysis by both flow cytometry and immunohistochemistry. Tumour sections were stained for vasculature and IdUrd. Each blood vessel was scored for the density of IdUrd-labelled cells surrounding it, using a semi-quantitative scoring system. Flow cytometry showed that the IdUrd labelling index and intensity decreased by approximately 50% after hydralazine. In tumour sections of control animals, 2.9% of vessels showed no IdUrd label. In contrast, after hydralazine almost 50% of vessels had no surrounding IdUrd labelling, whereas after nicotinamide there were fewer vessels with low labelling and a higher median score. In conclusion, changes of tumour perfusion by pharmacological agents is reflected in changes in tumour-cell labelling by the thymidine analogue IdUrd, suggesting that IdUrd labelling could be used to indicate perfusion in individual vessels in human tumours.

Animals↗
PubMed1999

The effect of preoperative radiation therapy on glucose utilization and cell kinetics in patients with primary rectal carcinoma.

BACKGROUND: Proliferating cells in neoplasms usually show rapid cell cycle times and high rates of glycolysis. Tumor glucose utilization (TuGluc), potential cell doubling time (Tpot), and the effect of radiotherapy (RT) were evaluated in patients with primary rectal carcinoma. METHODS: 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) was administered and dynamic positron emission tomography (PET) performed to determine TuGluc. Cell kinetics were measured with flow cytometry after labeling with iodo-deoxy-uridine. Two groups of patients were investigated prospectively: 1) those patients undergoing surgery only and 2) those patients undergoing surgery after receiving 30 gray of RT. Twenty consecutive patients with a cT3-NX-M0 tumor and age > 50 years were selected and randomized. One patient was excluded because of unexpected liver metastases and another had incomplete data. RESULTS: At baseline, the TuGluc for Group 1 was 222+/-104 nmol/mL/minute (mean +/- 1 standard deviation), and was 215+/-126 nmol/mL/minute for Group 2 (P > 0.8). After RT TuGluc decreased to 77+/-39 nmol/mL/minute (P = 0.008). Tpot was 3.4+/-1.2 days for Group 1 and 2.6+/-2.0 days for Group 2 at baseline (P > 0.2). Two weeks after RT, Tpot slowed to 5.7+/-3.6 days (P = 0.04). A weak negative correlation (correlation coefficient = -0.36) was found between TuGluc and Tpot. After RT, the proportion of labeled cells had not changed from baseline levels (P > 0.2), suggesting undisturbed proliferation, but the DNA synthesis time had increased. The significant decrease of TuGluc indicated cell loss. CONCLUSIONS: Tumor FDG uptake and cell kinetics are not correlated strongly in rectal carcinoma. Preoperative RT results in an overall loss of tumor cells (tumor reduction) and an increase in Tpot, although proliferation of the viable cell fraction is maintained.

Cell Cycle↗
PubMed1999

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis.

PURPOSE: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patients treated by conventional radiotherapy. MATERIALS AND METHODS: Data from 11 different centers were pooled. Inclusion criteria were such that the patients received radiotherapy alone, and that the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) intravenously prior to treatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were subsequently calculated from flow cytometry data, obtained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own flow cytometry analysis. RESULTS: From the 11 centers, a total of 476 patients conforming to the inclusion criteria were analyzed. Median values for overall time and total dose were 49 days and 69 Gy, respectively. Fifty one percent of patients had local recurrences and 53% patients had died, the majority from their disease. Median follow-up was 20 months; being 30 months for surviving patients. Multivariate analysis revealed that T-stage, maximum tumor diameter, differentiation grade, N-stage, tumor localization and overall time correlated with locoregional control, in decreasing order of significance. For the cell kinetic parameters, univariate analysis showed that only LI was significantly associated with local control (P=0.02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer values did worse, but this was not significant (P=0.06). Tpot showed no trend (P=0.8). When assessing survival in a univariate analysis, neither LI nor Tpot associated with outcome (P=0.4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P=0.02). In the multivariate analysis of local control, LI lost its significance (P=0.16). CONCLUSIONS: The only pretreatment kinetic parameter for which some evidence was found for an association with local control (the best end-point for testing the present hypothesis) was LI, not Tpot, and this evidence disappeared in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using flow cytometry, only provide a relatively weak predictor of outcome after radiotherapy in head and neck cancer.

Analysis of Variance↗
PubMed1998

Relationship between potential doubling time (Tpot), labeling index and duration of DNA synthesis in 60 esophageal and 35 breast tumors: Is it worthwhile to measure Tpot?

BACKGROUND: In recent years Tpot (potential doubling time) has been measured before treatment in human tumors in an attempt to estimate the proliferation taking place during a course of irradiation. Tpot is defined as Ts/LI, where Ts is the duration of DNA synthesis and LI is the labeling index (proportion of cells synthesizing DNA). Ts is more difficult to measure than LI, so the question arises whether variation introduced during the determination of Ts is compensated by the theoretically better relevance of the quotient Tpot than of LI alone. It is not clear from comparisons with clinical outcome whether Tpot is a useful indicator of proliferation or whether LI is more prognostic, as suggested by a currently ongoing multicenter analysis elsewhere. Therefore, we investigated intercomparisons between Tpot and its components LI and Ts in two in their proliferation rates contrasting types of tumor where multiple biopsies were taken from each tumor. MATERIALS AND METHODS: Sixty patients with esophageal carcinoma and 57 patients with breast cancer were included in this study. All patients were injected with IUdR 6-8 h before surgery. From each tumor three to five biopsies were taken at surgery. Using flow cytometry, LI and Ts were measured on all biopsies in order to calculate Tpot. Logarithmic transformations of the distributions were used to examine correlations. Kappa-tests were used to assess how reliable an LI value could be in predicting the corresponding Tpot. RESULTS: Ts and LI were not completely independent, based on the within-tumor coefficients of variation (CVw). The ratio of between-tumor coefficient of variation (CVb) to the CVw suggested that the discriminative power of Tpot was higher than LI for esophagus, but the reverse in breast tumors, which had a larger range. Pearson correlation coefficients were high for log Tpot versus log LI in both types of tumor, but the predictive power was low, as shown by kappa-values of only 0.3-0.41 starting with LI and trying to predict the corresponding value of Tpot. Increasing widths of a central 'gray zone' were investigated for improved discrimination between fast and slow proliferation. Multiples of the within-tumor standard deviation, equally on each side of the median, were used to vary the width of the gray zone. Without a gray zone no more than 70% successful matching was obtained in esophagus tumors, compared with 80% in breast tumors. However, by excluding about half of the esophageal tumors an 80% success rate was achieved. In breast tumors over 90% matching was obtained more easily, keeping 80% of the tumors classifiable. For both tumor types correlations between Ts and Tpot were weak, with a trend towards short Ts associated with short Tpot and also with low LI. The latter correlation was significant for esophageal tumors and resulted in Tpot values having a smaller range than the LIs. CONCLUSION: Although there were good correlation coefficients between Tpot and LI, the predictive power of either from the other was not reliable, except by excluding a significant number of tumors close to the medians. The predictive value of LI for Tpot was higher for breast tumors because the spread in cell kinetic measurements was wide. Until more clinical data become available on outcome in comparison with LI or Tpot, it is still worthwhile to measure Tpot and to assess the prognostic value of both LI and Tpot in relation to outcome.

Adenocarcinoma↗
PubMed1998

Does sucralfate reduce the acute side-effects in head and neck cancer treated with radiotherapy? A double-blind randomized trial.

BACKGROUND AND PURPOSE: We evaluated sucralfate, well-known in the treatment of gastric ulcers, in relation to its possible reduction of radiation-induced acute complications in the treatment of head and neck cancers. MATERIALS AND METHODS: One hundred two patients were randomized in a double-blind placebo-controlled prospective setting. All patients were treated to a minimum dose of 55 Gy in 5 weeks. Oral intake of sucralfate was started at the beginning of radiotherapy and continued during the whole treatment at a dose of 1 g six times a day. All patients were scored according to a scoring system developed in our department. Weight was checked once a week. RESULTS: Comparing the time course of the mean scores for subjective intolerance, mucositis, dysphagia, dermatitis and nausea, no statistically significant differences between the two treatment arms (sucralfate, n = 38; placebo, n = 45) were observed. The mean weight loss in the sucralfate arm was 1.6 +/- 3.4 kg while it was 1.3 +/- 2.0 kg in the placebo arm. Apart from gastrointestinal upset, the administration of sucralfate did not cause any side-effects. CONCLUSION: This trial produced no clinical evidence indicating that the oral intake of sucralfate reduces the acute radiation-induced side-effects. Therefore, we do not recommend the prophylactic use of sucralfate in patients with head and neck cancer treated by radiotherapy.

Acute Disease↗
PubMed1997

Is pulsed dose rate more damaging to spinal cord of rats than continuous low dose rate?

BACKGROUND AND PURPOSE: Theoretical calculations suggest that pulsed dose-rate irradiation (PDR) should have approximately the same effectiveness as continuous low dose-rate (CLDR) when the same total dose is given in the same overall time, unless large doses per pulse (> 2 Gy) are used and/or non-exponential or very short half-times of repair (< 0.5 h) are present in the irradiated tissues. However, few animal experiments have been reported to test this theory, and some of them gave contradictory results. We have carried out experiments to determine whether PDR irradiation of 18 mm of cervical spinal cord in the rat was more or less effective than CLDR at 0.5-1 Gy/h, when the overall average dose rate during each day of PDR was close to the overall CLDR average dose rate. MATERIALS AND METHODS: PDR was simulated at a within-pulse dose rate of 4 Gy/h by filtered 18 MV X-rays from a linear accelerator. Two PDR schedules were used, 0.69 Gy at 1 h repetition (9 pulses per day) and 2 Gy at 3 h repetition (4 pulses per day), with overnight intervals of 16 and 15 h, respectively. The CLDR was delivered from iridium-192 wires in two concentric rings around a collar designed to fit the necks of rats so that they could eat and drink during the 72 h that was always the duration of the CLDR. Dose rate was then proportional to total CLDR dose. A range of doses was used to obtain dose response-curves, with a 15 Gy top-up dose (at 2 Gy/min, HDR) given on the day after the end of the PDR or CLDR irradiations. Animals were observed for at least 9 months to see whether fore-limb myelopathy developed. A total of 6-8 rats was irradiated per dose point, in two sets of experiments at an interval of 12 months. RESULTS: A set of 2 Gy fractions (at HDR) given daily, followed by the same top-up dose of 15 Gy at HDR, was available from a previous experiment for planning. Its ED50 was 61.2 Gy. The ED50 values found for the PDR schedules with 2 Gy at 3 h and 0.69 Gy at 1 h were 59.9 and 60.2 Gy, respectively. These were just 2% more effective than the daily HDR fractions, similar to expectations from theory if two components of repair are present. However, the CLDR irradiations resulted in no myelopathy even after doses up to 68 Gy at 0.94 Gy/h.. Thus PDR over 7 days (not at nights) appears to be more effective than CLDR over 3 days, with an effective dose-modifying factor of at least 1.1 to 1.17. DISCUSSION AND CONCLUSIONS: Reasons for this absence of effect with CLDR in these experiments are discussed, the most likely explanation being that a substantial component of repair with very short T1/2 (< 0.5 h) was present in spinal cord of these rats. There is evidence from other experiments elsewhere and in our laboratory for such a fast component of repair.

Animals↗
PubMed1997

Non-invasive tumour perfusion measurement by dynamic CT: preliminary results.

In 18 patients the perfusion of a malignant head and neck tumour was estimated using contrast enhanced dynamic computed tomography. The mean estimated perfusion was 75.5 ml/100 g/min, varying between 27.9 and 131.9. Eleven patients were treated with radiation therapy; the obtained perfusion rates were significantly different between tumours with a favourable and those with an unfavourable early outcome.

Adult↗