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S Dische

Publications and source records attributed to S Dische.

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

Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. CHART Steering committee.

BACKGROUND AND METHOD: A randomised controlled trial in locally advanced non-small cell lung cancer (NSCLC), compared CHART which employs 36 fractions of 1.5 Gy 3 times per day to give 54 Gy in 12 consecutive days with conventional radiotherapy-30 fractions of 2 Gy to a total dose of 60 Gy in 6 weeks. A total of 563 patients were entered between April 1990 and April 1995. This report is based upon the data updated to 1 April 1998. RESULTS: The analysis of the mature data shows that the benefits previously reported have been maintained. Overall there was a 22% reduction in the relative risk of death, which is equivalent to an absolute improvement in 2 year survival of 9% from 20 to 29% (P = 0.008) and a 21% reduction in the relative risk of local progression (P = 0.033). In the large subgroup of patients with squamous cell cancer which accounted for 81% of the cases, there was a 30% reduction in the relative risk of death, which is equivalent to an absolute improvement in 2 year survival of 13% from 20 to 33% (P = 0.0007) and a 27% reduction in the relative risk of local progression (P = 0.012). Furthermore, in squamous carcinoma there was a 25% reduction in the relative risk of local and/or distant progression (P = 0.025) and 24% reduction in the relative risk of metastasis (P = 0.043). There was no evidence that CHART gave more or less benefit in any other subgroup. CONCLUSION: This analysis of mature data confirms that CHART is superior to conventional radiotherapy in achieving local tumour control and survival in locally advanced NSCLC. This demonstrates the importance of cellular repopulation as a cause of failure in the radiotherapy of NSCLC. The reduction in the risk of metastasis confirms that improved local tumour control, even in lung cancer, can reduce the incidence of metastasis. This trial shows that control of local tumour can lead to an improvement in long term survival.

Adult↗
PubMed1999

Carcinoma of the cervix and the use of hyperbaric oxygen with radiotherapy: a report of a randomised controlled trial.

BACKGROUND AND PURPOSE: A randomised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980. Apart from an abstract giving an interim report in 1977, results have not been published. MATERIAL AND METHODS: In a four arm study, 335 patients were randomised to treatment in 10 or 28 fractions, in hyperbaric oxygen or in air. Data is available concerning 327 cases and this has been analysed. RESULTS: There was no advantage in tumour control shown with the use of hyperbaric oxygen. There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when, using 10 fractions, a total dose of 45 rather than 40 Gy was achieved. For late intestinal morbidity, the fractionation sensitivity (alpha/beta ratio) was calculated to be 4.3 Gy and the steepness of the dose response curve (gamma50) to be 2.6. CONCLUSIONS: Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes. Important data regarding late radiation morbidity has been revealed.

Adult↗
PubMed1999

Repair halftimes estimated from observations of treatment-related morbidity after CHART or conventional radiotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: The CHART (Continuous Hyperfractionated Accelerated Radiotherapy) head and neck cancer fractionation schedule delivered 54 Gy in 36 fractions on 12 consecutive days and this was compared in a randomised controlled trial with conventional fractionation delivering 66 Gy in 33 fractions over 6-7 weeks. Patients receiving CHART experienced statistically significantly less treatment-related morbidity after 6 months than patients receiving conventional fractionation. However, this improved tolerance was much less than anticipated from existing knowledge of dose-fractionation effects on late-responding normal tissues. Here, the experience from the CHART study is analysed and repair halftimes for three types of late treatment-related morbidity of human tissues are estimated. PATIENTS AND METHODS: The CHART trial was open for patient accrual from March 1990 to April 1995 and a total of 918 patients in 11 participating centres were randomised. All patients were followed at regular intervals for a minimum of 5 years or until the time of death. At each follow-up, a number of treatment-related morbidity items were evaluated and scored prospectively. Data for three late endpoints are analysed here: laryngeal oedema, skin telangiectasia and subcutaneous fibrosis. Differences in the incidence of these endpoints in the two trial arms were quantified by means of the ratio of hazard rates in a Cox proportional hazards model. Monte Carlo sampling was performed from distributions of fractionation sensitivity (quantified by the alpha/beta-ratio) and steepness of the dose-response curve (quantified by the normalised dose-response gradient, gamma50) with means and standard deviations derived from the literature. Each pair of values were used to convert a Monte Carlo sampled estimate of the difference in biological effect into an estimate of the repair halftime. From the distribution of 1000 Monte Carlo samples, the mean repair halftime and its 95% confidence interval were estimated. RESULTS: The estimated repair halftimes, with 95% confidence intervals in parentheses, were 4.9 h (3.2, 6.4) for laryngeal oedema, 3.8 h (2.5, 4.6) for skin telangiectasia and 4.4 h (3.8, 4.9) for subcutaneous fibrosis. Calculations show that these repair halftimes are consistent with the observations from two published randomised controlled trials of altered fractionation in head and neck cancer, the EORTC 22791 and 22851 trials. CONCLUSIONS: These long repair halftimes for late effects in human normal tissues have to be considered in order to gain the full benefit from fractionation schedules employing multiple fractions per day.

Carcinoma, Squamous Cell↗
PubMed1999

Revealing morbidity.

Explore the source record for details and available documents.

Combined Modality Therapy↗
PubMed1999

Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine.

Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.

Anticarcinogenic Agents↗
PubMed1999

The CHART regimen and morbidity.

In 1984, when the CHART regime was devised, it was predicted that acute reactions in skin and mucosae would be more severe but that there would be a considerable reduction of late effects in normal tissues. The findings from the pilot study conducted from 1985 to 1990 and from the randomized trials, which entered cases from 1990 to 1995, are reviewed. With CHART, it was found that acute mucosal reactions were more severe but tolerable and recoverable. Unexpectedly, acute skin reactions were reduced rather than increased. Late reactions in the central nervous system have led to a dose restriction of 40 Gy. Effects in other normal tissues were significantly reduced but the sparing effect was less than that predicted. This can perhaps be explained by a half-time of repair of sublethal injury in human tissues in excess of 4 h.

Dose Fractionation, Radiation↗
PubMed1998

The breast radiation injury litigation and the clinical oncologist.

A number of women with breast cancer believed they were suffering injury because radiotherapy had been given negligently. In March 1995, their solicitors were permitted by the High Court, to select 10 cases in order to further a group action. In the legal exchanges which followed, the principal issues put forward by the plaintiffs went through a number of modifications until finally, in December 1997, they were abandoned. Two cases came to trial and after a hearing of 21 days, the Judge found no negligence. Clinical oncologists should be aware of the course of the litigation and consider the lessons to be learned.

Breast Neoplasms↗
PubMed1997

Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee.

BACKGROUND: Human tumour cells can proliferate rapidly, and giving radiotherapy in many small fractions may reduce long-term normal-tissue morbidity. In response to these observations, we developed the CHART (continuous hyperfractionated accelerated radiotherapy) regimen, which uses thirty-six small fractions of 1.5 Gy given three times per day, to give 54 Gy in only 12 consecutive days. We report the long-term follow-up of a trial of CHART versus conventional radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: 563 patients were entered by thirteen centres between April, 1990, and March, 1995. We included patients with NSCLC localised to the chest with a performance status of 0 or 1 in whom radical radiotherapy was chosen as the definitive management. Patients were randomly allocated in a 3:2 ratio to CHART or conventional radiotherapy. The latter was thirty fractions of 2 Gy to a total dose of 60 Gy in 6 weeks. RESULTS: The groups were well matched for possible prognostic factors. Overall there was a 24% reduction in the relative risk of death, which is equivalent to an absolute improvement in 2-year survival of 9% from 20% to 29% (p = 0.004, 95% CI 0.63-0.92). Subgroup analyses (predefined) suggest that the largest benefit occurred in patients with squamous cell carcinomas (82% of the cases), in whom there was a 34% reduction in the relative risk of death (an absolute improvement at 2 years of 14% from 19% to 33%). During the first 3 months, severe dysphagia occurred more often in the CHART group than in the group on conventional radiotherapy (19 vs 3%). Otherwise, there were no important differences in short-term or long-term morbidity. INTERPRETATION: CHART compared with conventional radiotherapy gave a significant improvement in survival of patients with NSCLC. Further improvement may be achieved with dose escalation in conformal radiotherapy, by the addition of cytotoxic chemotherapy, and by hypoxic cell radiosensitisation.

Adult↗
PubMed1997

Continuous hyperfractionated accelerated radiotherapy (CHART) in localized cancer of the esophagus.

PURPOSE: To assess the efficacy and toxicity of continuous hyperfractionated accelerated radiotherapy (CHART) in locoregional control compared with a historical group of patients treated with conventionally fractionated radical radiotherapy. METHODS AND MATERIALS: Between 1985 and 1994, 54 patients with localized esophageal cancer were treated with CHART. Twenty-eight patients received CHART alone (54 Gy in 36 fractions over 12 consecutive days) and 15 were given intravenous mitomycin C and cisplatin on days 10 and 13, respectively. Eleven patients received 40.5 Gy in 27 fractions over 9 days, followed by a single high-dose-rate intraluminal brachytherapy insertion of 15 Gy at 1 cm. RESULTS: Acute toxicity was well tolerated and dysphagia was improved in 35 patients (65%), with 28 (52%) eating a normal diet by week 12. This compares with an improvement in dysphagia score in 72% of the conventionally treated group. The median duration of relief of dysphagia was 7.8 months (range 0-41.4) in the CHART group compared with 5.5 months (range 0-48) in the controls. Strictures developed in 29 patients (61%) and 18 were confirmed on biopsy to be due to recurrent disease. Median survival was 12 months (range 0.5-112) in the CHART group and 15 months (range 3.6-56) in the control patients. CONCLUSION: CHART is well tolerated and achieves a high rate of local control. Palliation in the short overall treatment time of esophageal cancer is an advantage in these patients whose median survival is only 12 months.

Adult↗
PubMed1997

A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: Continuous, hyperfractionated, accelerated radiotherapy (CHART) has shown promise of improved tumour control and reduced late morbidity in pilot studies and has now been tested in a multicentre randomised controlled clinical trial. MATERIAL AND METHODS: Patients with squamous cell cancer in the main sites within the head and neck region with the general exception of early T1 N0 tumours were entered into the study by 11 centres. There was a 3:2 randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions over 6.5 weeks. A total of 918 patients were included over a 5 year period from March 1990. RESULTS: ACUTE MORBIDITY: Acute radiation mucositis was more severe with CHART, occurred earlier but settled sooner and was in nearly all cases healed by 8 weeks in both arms. Skin reactions were less severe and settled more quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table analyses of loco-regional control, primary tumour control, nodal control, disease-free interval, freedom from metastasis and survival showed no evidence of differences between the two arms. In exploratory subgroup analyses there was evidence of a greater response to CHART in younger patients (P = 0.041) and poorly differentiated tumours appeared to fare better with conventional radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4% of patients after conventional radiotherapy. The incidence of chondritis or cartilage necrosis was similar in both arms. Life table analysis showed evidence of reduced severity in a number of late morbidities in favour of CHART. These were most striking for skin telangiectasia, superficial and deep ulceration of the mucosa and laryngeal oedema. CONCLUSION: Similar local turnout control was achieved by CHART as compared with conventional radiotherapy despite the reduction in total dose from 66 to 54 Gy supporting the importance of repopulation as a cause of radiation failure. The effects seen in advanced laryngeal cancer and those related to histological differentiation need further study. Reduced late morbidity is a factor which together with patient preference should be considered in the decision as to the programme of radiotherapy to employ in the curative treatment of head and neck cancer.

Adult↗
PubMed1997

Accelerated radiotherapy, carbogen and nicotinamide (ARCON) in locally advanced head and neck cancer: a feasibility study.

BACKGROUND AND PURPOSE: ARCON (Accelerated Radiotherapy, CarbOgen, Nicotinamide) achieves a large therapeutic gain in rodents. A phase I/II study was therefore undertaken to determine its feasibility in patients with locally advanced head and neck cancer. MATERIALS AND METHODS: The accelerated regime CHART was used in 35 patients given carbogen and/or nicotinamide with 11 small volume fractions. Eight patients received carbogen, 12 received nicotinamide and 15 were treated with ARCON. Treatment compliance, side-effects and acute mucositis were monitored in all cases. RESULTS: All patients underwent CHART as intended. In the 23 patients receiving carbogen, two failed to complete treatment. Compliance with nicotinamide was much lower. Out of 25 patients, only 52% received 10-11 doses of the 80 mg/kg/day of the drug. The most common side-effect was nausea and vomiting, which responded to standard anti-emetics in almost half of the patients. Historical comparisons with the CHART head and neck trials indicate that there was no increase in the severity of acute mucositis in any of these patients. Although the observation period is not sufficiently long to be definitive (median 20 months) there is no evidence of an increase in late normal tissue reactions. CONCLUSIONS: ARCON using CHART as the radiotherapy protocol is feasible in patients with advanced head and neck cancer. However, we are concerned about the low compliance rate in our patients, which is far lower than that reported elsewhere. The implications are discussed together with identifying strategies for increasing compliance.

Administration, Oral↗
PubMed1997

Fractionation in radiotherapy: a view from the clinic.

A century of the evolution of the fractionation of radiotherapy has brought clinical oncologists to the testing of protocols in randomized controlled clinical trials. The British Institute of Radiology's pioneering trials, together with more recent studies, are described and future developments suggested.

Dose Fractionation, Radiation↗
PubMed1996

The dental problems of patients with head and neck cancer treated with CHART.

Between 1985 and 1990, 99 head and neck cancer patients were treated at Mount Vernon Centre for Cancer Treatment in a CHART pilot study. The aims of this retrospective review were to obtain baseline data for this population on their pretreatment dental status and to determine the extent to which our conservative policy of teeth preservation is being realised. This is of particular interest because of the believed sparing of late normal tissue effects by CHART compared with conventional fractionation. Prior to treatment, 40% of patients were edentulous, and prophylactic dental clearance was avoided in 59% of the remaining (dentate) patients. Following radiotherapy, only 21% of dentate patients subsequently lost all their remaining teeth. The proportion of patients with full or partial upper dentures increased from 61% pretreatment to 76% post-treatment; the corresponding increase in lower dentures was 46% to 66%. However, actual usage of dentures decreased somewhat. There was only one documented case of (minor) osteo-radionecrosis of the mandible which resolved with conservative care. The greater use in our patients of prophylactic measures, in particular, chlorhexidine and fluoride mouthwashes seemed indicated.

Adult↗
PubMed1996

Randomised multicentre trials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. CHART Steering Committee.

While radiotherapy is proceeding, tumour cells may proliferate. The use of small individual doses reduces late morbidity. Continuous hyperfractionated accelerated radiation therapy (CHART), which reduces overall treatment from 6-7 weeks to 12 days and gives 36 small fractions, has now been tested in multicentre randomised controlled clinical trials. The trial in non-small-cell lung cancer included 563 patients and showed improvement in survival; 30% of the CHART patients were alive at 2 years compared with 20% in the control group (P = 0.006). In the 918 head and neck cases, there was only a small, non-significant improvement in the disease-free interval. In this interim analysis there was a trend for those with more advanced disease (T3 and T4) to show advantage; this will be subject to further analysis when the data are more mature. The early mucosal reactions appeared sooner and were more troublesome with CHART, however they quickly settled; so far no difference in long-term morbidity has emerged. These results support the hypothesis that tumour cell repopulation can occur during a conventional course of radiotherapy and be a cause of treatment failure.

Adult↗
PubMed1996

The effect of radiotherapy on urethral obstruction from carcinoma of the prostate.

OBJECTIVE: To assess the impact of radiotherapy on the relief of complete bladder outlet obstruction requiring catheterization secondary to prostatic carcinoma. PATIENTS AND METHODS: From a consecutive series of 151 patients treated with radiotherapy for localized carcinoma of the prostate, 19 (12.6%; median age 72 years, range 59-83) who had an indwelling catheter in situ at the time of irradiation because of urinary retention, were analysed retrospectively and grouped according to the stage and grade of tumour and the irradiation dose delivered. RESULTS: The catheter was removed following radiotherapy in all but two patients, who both had stage 4 tumours, and normal urinary function was restored. The grade and stage of tumour did not influence the duration of catheterization. The median time from completion of radiotherapy to catheter removal was 10 weeks (range 0-46). Recatheterization was required in two patients at 3 and 64 months after radiotherapy and three patients, including these two, required transurethral prostatectomy (TURP) to relieve outlet obstruction. CONCLUSION: Prostatic radiotherapy is effective in relieving bladder neck obstruction caused by prostate cancer. Most patients will achieve normal urinary function without requiring TURP after treatment.

Aged↗
PubMed1996

Time course from first symptom to treatment in patients with non-small cell lung cancer referred for radiotherapy: a report by the CHART Steering Committee.

BACKGROUND: Only a small proportion of patients with non-small cell lung cancer (NSCLC) attending radiotherapy centres were suitable for inclusion in a randomised trial which compared continuous hyperfractionated accelerated radiotherapy (CHART) with conventional radical radiotherapy. As this was thought to be partly due to delays in the referral of patients to clinical oncologists, a prospective study was performed to determine the interval between first report of symptoms and first radiotherapy treatment in patients with NSCLC. METHODS: The time course from first symptom to treatment was determined in all patients with NSCLC attending 10 cancer centres for radiotherapy to a primary tumour in a three month period. RESULTS: Only 5% of 484 patients were suitable for the trial of radical radiotherapy. The principal causes for exclusion were poor general condition (37%), too large a tumour (27%), and extrathoracic metastases (19%). The median time from first symptom to diagnosis was 13 weeks, from first symptom to first treatment 19 weeks, and from diagnosis to first treatment five weeks. In a quarter of the patients these intervals were greater than 25,33 weeks, and nine weeks, respectively. CONCLUSION: The reason for these long intervals needs investigation since earlier diagnosis and more immediate referral for consideration of treatment might increase the number of patients with NSCLC suitable for radical radiotherapy.

Aged↗