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Biomedical subjects

P Scalliet

Publications and source records attributed to P Scalliet.

At least 37 records · Page 2Linked to original sources
PubMed1999

The effect of 2'-2' difluorodeoxycytidine (dFdC, gemcitabine) on radiation-induced cell lethality in two human head and neck squamous carcinoma cell lines differing in intrinsic radiosensitivity.

PURPOSE: The present study investigated in vitro radio-enhancement by gemcitabine (dFdC) in two head and neck squamous cell carcinomas with different intrinsic cellular radiosensitivity. MATERIALS AND METHODS: Radiosensitive (SCC61, SF2=0.16) and radioresistant (SQD9, SF2=0.49) human head and neck squamous cell carcinomas were used. Confluent cells were incubated with dFdC and irradiated in drug-free medium with a single dose of 250 kV X-rays (0-12Gy). Cell survival curves were corrected for the toxicity of the drug alone. RESULTS: In both cell lines, radio-enhancement was observed with 5 microM dFdC incubated for 3 h prior to irradiation. Dose modification factors (DMF) at a surviving fraction level of 0.5 reached 1.3 (95% CI 1.1-1.6) and 1.5 (95% CI 1.4-1.5) for SQD9 and SCC61 cells, respectively. Radio-enhancement was associated with a modest increase in the alpha term of the linear-quadratic model. In SQD9 cells, radio-enhancement increased with dFdC incubation time. At 24h, DMF reached a value of 1.5 (95% CI 0.9-3.2). In SCC61 cells at 24h, DMF reached a value of 1.1 (95% CI 0.9-1.2). In both cell lines, radio-enhancement increased with dFdC concentration up to 5-10 microM from which values it levelled off up to 100 microM. CONCLUSIONS: The data indicated that dFdC induced a modest radio-enhancement in both cell lines. For a short incubation time, dFdC did not radio-enhance preferentially the more radio-resistant cells, whereas the opposite was observed for a longer time. In both cell lines, radio-enhancement was saturated above a dFdC concentration of 5-10 microM.

Carcinoma, Squamous Cell↗
PubMed1999

Bone marrow content measured in radioimmune bone marrow scintigraphy: intra- and inter-observer variability.

The aim of this study was to assess the possible quantification of vertebral residual bone marrow content relative to the bone marrow content of a non-irradiated vertebra. This method is based on the vertebral count activity, measured using radioimmune bone marrow scintigraphy. First, however, we had to evaluate intra- and inter-observer variability. In three patients who underwent radioimmune bone marrow scintigraphy, two independent observers measured the count density in 51 (15 lumbar and 36 thoracic) vertebrae using a manually drawn region of interest. To evaluate intra- and inter-observer variability, we calculated the means and standard deviations of the differences between measurements. Bland-Altman plots were drawn for all vertebrae as well as for three subgroups of vertebrae (the upper thoracic spine, D1-D6; the lower thoracic spine, D7-D12; and the lumber spine, L1-L5). For all vertebrae, the mean (+/- S.D.) difference, expressed as a percentage of the overall mean, was -0.44 +/- 3.3% for observer 1 and -0.3 +/- 2.1% for observer 2 for intra-observer variability; inter-observer variability varied from 0.55 +/- 3.9% to 1.28 +/- 3.7%. On the Bland-Altman plots, the data points were evenly distributed above and below the 0-line and the linear regression equations matched the line of equality almost perfectly. This pattern was observed for all the vertebrae as well as for the subgroups of vertebrae. In conclusion, our results show that the intra- and inter-observer variabilities are not great, confirming that this technique is simple and robust and can be used for further quantification of bone marrow content in the axial skeleton.

Adult↗
PubMed1999

Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice.

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.p. 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% CI 13.33-15.66 Gy). With a 3-h interval between administration of dFdC and irradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the corresponding value with a 48-h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy). Our data also suggested a possible effect of dFdC on radiation-induced esophageal toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before any routine use of combined dFdC and radiotherapy in the thoracic region.

Animals↗
PubMed1998

Age has no impact on acute and late toxicity of curative thoracic radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy is a treatment method frequently employed in the management of thoracic tumours. Although the highest incidence of these tumours is found in elderly people, tolerance to radiotherapy is not well documented in older age groups. Many physicians are tempted to alter the radiotherapy planning in a population with a supposed lower life expectancy in order to prevent acute reactions whereas late reactions are often ignored. The current study aimed to determine the influence of age on the frequency and severity of acute and late side-effects and also whether the prognosis of tumours sufficiently differed between ages to justify different attitudes towards their management. MATERIALS AND METHODS: Data from 1208 patients receiving chest irradiation and included in arms designed with RT of six EORTC randomized trials were evaluated. Data were extracted by a computer program elaborated for each study and were merged in a single database for analysis. Patients were split into six age ranges from 50 to 70 years and over. Survival and late toxicity were calculated with the Kaplan-Meier method and comparison between age groups was performed with the logrank test. The gamma-statistic test was used to test the impact of age on acute toxicity occurrence. RESULTS: Survival adjusted for the primary location of the tumour was comparable in each age group (P = 0.82). Data regarding age and acute toxicity were available for 1208 patients who experienced 640 grade > or =1 toxicities. The difference in distribution over age was not significant for acute nausea, dyspnea, oesophagitis, weakness and WHO performance status alteration. Weight loss was significantly different with regards to age with a trend toward increased weight loss in older age groups (P = 0.002). To minimize actuarial bias, only patients surviving more than 90 days were analyzed for late effect risks. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first and second line treatments. In such conditions, 1082 grade > or =1 late toxicities were recorded in 935 patients of 1106 available for analysis. The mean time to complication was 13 months and was similar in all age groups. Forty percent of patients were free of complication at 4 years, the logrank test showing no significant difference between age groups (P = 0.57). For grade >2 side-effects, the calculation did not show any difference between each age group (P = 0.1). A detailed analysis of late dyspnea and late weakness studied with the same method did not demonstrate any difference between age groups. Only grade >2 late oesophagitis demonstrated a significant trend to be more frequent in older patients (P = 0.01), but this difference disappeared after adjustment on study (P = 0.32). CONCLUSION: The absence of toxicity observed in the current study regardless of age reinforces the conviction that age per se is not a sufficient reason to exclude patients in good general condition with thoracic tumour from curative radiotherapy when medically indicated.

Actuarial Analysis↗
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↗
PubMed1998

Comparison of external radiotherapy, laser microsurgery and partial laryngectomy for the treatment of T1N0M0 glottic carcinomas: a retrospective evaluation.

PURPOSE: The aim of this study was to retrospectively compare the efficacy and functional results of three treatment options for T1N0M0 glottic carcinomas applied in a single institution. MATERIALS AND METHODS: One hundred six charts of patients with biopsy-proven T1N0M0 glottic carcinomas treated between 1979 and 1995 were reviewed. There were 81 T1a and 25 T1b tumors. Forty-one patients were treated by radiotherapy (RT) (median dose of 64 Gy), 34 patients were treated by partial laryngectomy (PL) and 31 patients were treated by laser microsurgery (L) of which 10 received postoperative RT for positive margins. In 18 patients, a perceptual voice rating on a visual scale was performed by the patients themselves, three non-speech specialists and two speech therapists. RESULTS: With a median follow-up time of 63.5 months, the 5- and 10-year loco-regional control probabilities reached 91 and 87%, respectively, without any difference between the treatment groups. After salvage laryngectomy, the 5- and 10-year loco-regional control probabilities reached 97% without any difference between the treatment groups. For the whole population, overall survival reached 78 and 62.4% at 5 and 10 years, respectively. The actuarial incidence of second primary reached 19% at 10 years. Regarding the quality of voice, overall there was a trend towards a worse satisfaction index, more hoarseness and more breathiness after PL than after L or RT. CONCLUSIONS: Our data suggested that assuming proper selection of patients, RT and L yielded similar outcomes and functional results. Local recurrence can be adequately salvaged by surgery. On the other hand, PL appeared to yield similar loco-regional control probability but with a worse quality of voice.

Actuarial Analysis↗
PubMed1998

Radiotherapy in the elderly.

Older patients with cancer are frequently victims of discriminatory treatment strategies according to parameters unrelated to the tumour itself. The general approach is influenced by the belief that good tolerance to radiotherapy might be compromised in older patients and that the course of cancer might be less aggressive in this age group. Substandard treatment is therefore often offered to older patients, although this attitude is supported neither by clinical nor by scientific evidence, but rather stems from a lack of specific knowledge of the actual cancer prognosis and the tolerance to radiotherapy in the elderly. In clinical practice advanced age may result in undertreatment, even though patients may have no other medical illness and no functional impairment. Some comorbid conditions which are more frequent in older patients may complicate the outcome of treatment. However, these impaired vital functions are not an intrinsic feature of the elderly. Overall, noncompliance in radiotherapy, related to comorbidity or technical condition, is rare. Short-term radiotherapy using a large daily fraction is often advocated in elderly patients; however, this should only be considered if a palliative treatment option has previously been selected due to the high risk of late side-effects. Acute side-effects often result in decreasing doses of radiotherapy. Data on acute tolerance of radiotherapy for different types of tumours did not demonstrate a radical difference in occurrence of toxicities. 'Reducing' radiotherapy is never a solution, unless the life expectancy of the patient is obviously so short that the tumour recurrence is unlikely to occur or at least to produce substantial morbidity before the patient has died from other causes.

Age Factors↗
PubMed1998

Tumour size in cancer of the cervix.

In a randomized trial comprising 204 patients with operable cervical carcinomas stages I and II, two low-dose rates in gynaecological brachytherapy were compared. Treatment consisted of Cs-137 uterovaginal application followed by surgery (either immediate or delayed). The results for the two dose rates have been published previously. The present paper concerns the correlation between outcome and tumour size. Tumour size was carefully estimated in two ways: by clinical examination under general anaesthesia and by measurements on the customized vaginal mould used for the brachytherapy. Ninety-one patients (45%) were classified as stage I, and 113 were classified as stage II proximal. The mean tumour size was 39 mm (range 15-64 mm). Cox's multivariate analysis indicated that the factors with a poor prognostic value were for survival: node involvement (N +) (p < 0.001), large tumour size (T +) (p < 0.001) and involvement of the endocervix (E +) (p <0.01); for event-free survival: N + (p <0.001), T + (p < 0.001); for local control; N + (p = 0.0001); for metastasis and regional relapse: N + (p < 0.001) and T + (p < 0.001). Stage was not a prognostic factor over the present range in either univariate or multivariate analysis. In this series tumour size is a powerful independent prognostic factor. It is therefore suggested that for the classification of cervical cancer and the indications for surgical staging and adjuvant treatment, tumour size should be taken into account.

Adult↗
PubMed1998

Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis.

PURPOSE: To investigate the effect of fludarabine (F-ara-A) and gemcitabine (dFdC), two radiosensitizing nucleoside analogues, on the induction and repair of DNA dsb after ionizing radiation. MATERIALS AND METHODS: Radiosensitization of mouse sarcoma SA-NH and FSA cells was studied using a clonogenic assay. Cell survival curves were fitted with the linear-quadratic model. DNA dsbs were detected by pulsed-field gel electrophoresis under neutral conditions. RESULTS: F-ara-A (100 micromol dm(-3) for 1 h prior to irradiation) induced a substantial radiosensitization in SA-NH cells with a dose modification factor of 2.0 for a surviving fraction of 0.5. In a FSA mouse sarcoma cell line, dFdC (5 micromol dm(-3) for 3 h prior to irradiation) induced a modest radiosensitization with a DMF of 1.2 for a surviving fraction of 0.5. Under similar experimental conditions, neither F-ara-A nor dFdC altered the yield of radiation-induced DNA dsbs in the dose range of 0-40 Gy. After a single dose of 25 Gy (SA-NH cells) or 40 Gy (FSA cells), neither the kinetics of repair nor the amount of residual damage was affected by F-ara-A or dFdC. CONCLUSIONS: For experimental conditions under which radiosensitization was observed, neither the induction nor the repair of DNA dsbs after ionizing radiation were affected by F-ara-A or dFdC.

Animals↗
PubMed1997

Age is not a limiting factor for radical radiotherapy in pelvic malignancies.

BACKGROUND AND PURPOSE: Pelvic radiotherapy (RT) toxicity in the elderly is poorly documented. We developed a study aiming to evaluate whether or not a limit of age could be identified beyond which toxicities in patients receiving pelvic RT were more frequent or more severe. MATERIAL AND METHODS: 1619 patients with pelvic cancers enrolled in nine EORTC trials, RT arms, were retrospectively studied. Patients were split into six age ranges from 50 years to 70 years and over. Survivals and late toxicity occurrence were calculated with the Kaplan-Meier method and comparison between age groups with the logrank test. A trend test was done to examine if chronological age had an impact on acute toxicity occurrence. RESULTS: Survival was comparable in each age group for prostate (P = 0.18), uterus (0.41), anal canal cancer (P = 0.6) and slightly better for the younger group of rectum cancer (P = 0.04). A total of 1722 acute and 514 late grade > or = 1 were recorded. Acute nausea/ vomiting, skin complications and performance status deterioration were significantly more frequent in younger patients. There was no trend toward more aged patients to experience diarrhea (P = 0.149) and after adjustment on RT dose, acute urinary complications were observed equally in each age range (P = 0.32). Eighty percent of patients were free of late complication at 5 years in each age range (P = 0.79). For the grade > 2 late side-effects, a plateau was observed after 1 year at near 9% without any difference (P = 0.06) nor trend (P = 0.13) between age-groups. CONCLUSION: Age per se is not a limiting factor for radical radiotherapy in pelvic malignancies.

Age Factors↗
PubMed1997

RBE variation as a function of depth in the 200-MeV proton beam produced at the National Accelerator Centre in Faure (South Africa).

BACKGROUND AND PURPOSE: Thorough knowledge of the RBE of clinical proton beams is indispensable for exploiting their full ballistic advantage. Therefore, the RBE of the 200-MeV clinical proton beam produced at the National Accelerator Centre of Faure (South Africa) was measured at different critical points of the depth-dose distribution. MATERIAL AND METHODS: RBEs were determined at the initial plateau of the unmodulated and modulated beam (depth in Perspex = 43.5 mm), and at the beginning, middle and end of a 7-cm spread-out Bragg peak (SOBP) (depths in Perspex = 144.5, 165.5 and 191.5 mm, respectively). The biological system was the regeneration of intestinal crypts in mice after irradiation with a single fraction. RESULTS: Using 60Co gamma-rays as the reference, the RBE values (for a gamma-dose of 14.38 Gy corresponding to 10 regenerated crypts) were found equal to 1.16 +/- 0.04, 1.10 +/- 0.03, 1.18 +/- 0.04, 1.12 +/- 0.03 and 1.23 +/- 0.03, respectively. At all depths, RBEs were found to increase slightly (about 4%) with decreasing dose, in the investigated dose range (12-17 Gy). No significant RBE variation with depth was observed, although RBEs in the SOBP were found to average a higher value (1.18 +/- 0.06) than in the entrance plateau (1.13 +/- 0.04). CONCLUSION: An RBE value slightly larger than the current value of 1.10 should be adopted for clinical application with a 200-MeV proton beam.

Animals↗
PubMed1997

Patient information about radiation therapy: a survey in Europe.

BACKGROUND AND PURPOSE: We performed a survey to evaluate the present status and means of information given to patients treated by radiotherapy. A short questionnaire was sent, with the help of ESTRO, to 746 European heads of department with a request to send specific documents used for informing the patient. Within 2 months (March and April 1996) we received 290 answers (39%) and 97 centres sent documents. MATERIALS AND METHODS: Analysis of the questionnaire and the documents was performed quantitatively with usual statistical methods and qualitatively with a socio-anthropological method of content analysis. RESULTS: Analysis of the questionnaire shows the major role of the radiation oncologist in giving information and writing documents. The 298 different samples sent from 97 centres represent a wide panel with a booklet of general information (59 booklets/57 centres), practical advice and specific explanations (177 documents/49 centres) and informed consent (36 documents/28 centres). The anthropological study was centred on the way information was given, evaluation of the patient's understanding and analysis of documents sent. CONCLUSION: This preliminary survey needs to be completed by a study, including the patient's point of view and needs, about the information given.

Humans↗
PubMed1997

Modern brachytherapy: current state and future prospects.

This article reviews the current trends and future developments in brachytherapy. Established techniques including interstitial and high-dose rate brachytherapy are discussed with particular reference to lung, oesophageal, cervical and endometrial cancer. Intra-operative high-dose rate brachytherapy and other new techniques are also mentioned.

Brachytherapy↗
PubMed1997

Kinetics of mouse jejunum radiosensitization by 2',2'-difluorodeoxycytidine (gemcitabine) and its relationship with pharmacodynamics of DNA synthesis inhibition and cell cycle redistribution in crypt cells.

Gemcitabine (dFdC), a deoxycitidine nucleoside analogue, inhibits DNA synthesis and repair of radiation-induced chromosome breaks in vitro, radiosensitizes various human and mouse cells in vitro and shows clinical activity in several tumours. Limited data are however available on the effect of dFdC on normal tissue radiotolerance and on factors associated with dFdC's radiosensitization in vivo. The purpose of this study was to determine the effect of dFdC on mouse jejunum radiosensitization and to investigate the kinetics of DNA synthesis inhibition and cell cycle redistribution in the jejunal crypts as surrogates of radiosensitization in vivo. For assessment of jejunum tolerance, the mice were irradiated on the whole body with 60Co gamma rays (3.5-18 Gy single dose) with or without prior administration of dFdC (150 mg kg-1). Jejunum tolerance was evaluated by the number of regenerated crypts per circumference at 86 h after irradiation. For pharmacodynamic studies, dFdC (150 or 600 mg kg-1) was given i.p. and jejunum was harvested at various times (0-48 h), preceded by a pulse BrdUrd labelling. Labelled cells were detected by immunohistochemistry on paraffin-embedded sections. DNA synthesis was inhibited within 3 h after dFdC administration. After an early wave of apoptosis (3-6 h), DNA synthesis recovered by 6 h, and crypt cells became synchronized. At 48 h, the labelling index returned almost to background level. At a level of 40 regenerated crypts, radiosensitization was observed for a 3 h time interval (dose modification factor of 1.3) and was associated with DNA synthesis inhibition, whereas a slight radioprotection was observed for a 48-h time interval (dose modification factor of 0.9) when DNA synthesis has reinitiated. In conclusion, dFdC altered the radioresponse of the mouse jejunum in a schedule-dependent fashion. Our data tend to support the hypothesis that DNA synthesis inhibition and cell cycle redistribution are surrogates for radiosensitization. More data points are however required before a definite conclusion can be drawn.

Animals↗
PubMed1997

[Oncology in relation to aging of the population].

The constant aging of the population has a profound impact on future health policies regarding cancer treatment, because age is the main single determinant for developing cancer. A new specialty is now emerging: geriatric oncology. So far, the very few data available indicate that elderly patients are often misstaged and therefore mistreated, as a result of the lack of appropriate instruments for the evaluation of the individual life expentancy. New instruments should be developed given the emergency situation created by the explosive increase in cancer incidence.

Aged↗
PubMed1996

Deep cerebral invasion by basal cell carcinoma of the scalp.

We report recurrent basal cell carcinoma of the scalp with deep cerebral invasion in an 82-year-old man. Plain films and CT showed extensive, full thickness, skull destruction at the vertex. Gadolinium-enhanced MRI revealed neoplastic invasion of the meninges and left cerebral hemisphere, down to the lateral ventricle. We postulate that tumour extended into the brain along perivascular spaces of transcerebral vessels. This hypothesis is supported by the cleft-like contrast enhancement on MRI.

Aged↗
PubMed1996

Influence of respiration on calculation and delivery of the prescribed dose in external radiotherapy.

During the delivery of the prescribed dose in external beam radiotherapy, respiration alters the patient's body outline and consequently the basis for dose calculations. The influence of this effect was studied on both healthy volunteers and patients. In a subgroup of volunteers, we measured that respiratory movements modify a person's thickness, in particular in the antero-posterior direction at the lower abdominal level, by more than 4% implying a variation in absorbed dose of more than 2%. In view of the I.C.R.U. requirements for absorbed dose accuracy, these variations must be taken into account. Extension of the study to a group of 160 patients confirmed that for a subgroup of about 25%, respiration induces an important deviation from the prescribed dose as dose calculations are based on a body outline taken at an unknown stage during the respiratory cycle. Our results indicate that dose calculations should be based on an average body outline which takes the respiratory movements into account.

Adolescent↗