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Biomedical subjects

S Dische

Publications and source records attributed to S Dische.

At least 37 records · Page 2Linked to original sources

The morbidity of salvage surgery following conventional radiotherapy and continuous, hyperfractionated accelerated radiotherapy (CHART).

A comparison was made of the morbidity of surgery for loco-regional recurrence in patients with advanced cancer of the head and neck region following continuous hyperfractionated accelerated radiotherapy (CHART), after conventional radiotherapy, and also in a group following surgery only as the primary treatment. Post-surgical morbidity occurred in 14 (77%) of the 18 patients treated with CHART, of whom 11 (78%) required a further surgical procedure. In the conventional group, morbidity occurred in 14 (58%) of the 24 patients, of whom 9 (64%) required further surgery. Finally, in the surgical group morbidity occurred in 13 (48%) of the 27 patients, of whom 7 (54%) required further surgery. Because of the many factors that may influence the chance of morbidity and of the small number of cases, considered statistical analysis is not meaningful and there must be caution in the interpretation of results. When allowance is made for the greater frequency of more advanced tumors and for sites in the oropharynx and oral cavity, where procedures associated with greater risk of complication were performed, the morbidity seen after surgery was performed upon CHART patients appeared to be no greater than when conventional radiotherapy had been given. As expected, the surgery only group showed less morbidity than either of the radiotherapy groups.

Adult

A review of hypoxic cell radiosensitization.

Despite an enormous laboratory and clinical effort, advance in patient care has not yet been achieved by hypoxic cell radiosensitization. The reasons for this are considered and suggestions made as to the future direction of work in this important field.

Cell Hypoxia

Experience with CHART.

Continuous, hyperfractionated, accelerated radiotherapy (CHART) has been used at the Mount Vernon Cancer Treatment Center since January 1985. Patients with head and neck tumors and those with locally advanced non-oat cell carcinoma of the bronchus have formed the large majority of the 263 patients treated. Early reactions in the mucosae of the mouth and pharynx have been pronounced, but all have healed, while those in the skin have been less severe than with conventional radiotherapy. An unexpected late morbidity was radiation myelitis in four patients, but in other tissues including the skin, mucosae, the connective tissues, and the salivary glands, late changes appear reduced compared to those after conventional radiotherapy. In 92 patients with squamous cell carcinoma of the major sites in the head and neck region, of whom 71 were in Stages T3 and T4, a complete regression at the primary site and nodes was achieved in 90%. This can be compared with 62% in similar patients previously treated with curative intent at Mount Vernon between 1980 and 1985; the difference was maintained in follow-up (p = 0.003). Of 76 assessable patients with non-oat cell carcinoma of the bronchus, a complete radiological response has been achieved in 40%, compared to 12% in a retrospective group; again the difference has been maintained in follow up (p = 0.0001). A 1-year survival of 60% can be compared to 40% in the retrospective group and a 2-year survival of 29% compared to 12% (p = 0.01). With a reduction of permitted dose to the spinal cord, CHART gives promise for improvement in tumor control and a reduction in late morbidity. These promising results have led to multi-center randomized controlled clinical trials in carcinoma at the head and neck and in non-oat cell carcinoma of the bronchus. In these studies, CHART is being compared with conventional fractionated radiotherapy.

Aged

The prognosis of Hodgkin's disease in older adults.

This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates.

Adult

Lung function and radiation response.

This study investigated whether impaired respiratory function affected the response to radiotherapy. A prospective study was performed in which lung function, arterial oxygen and haemoglobin concentration were examined, before treatment with radical radiotherapy, in 141 patients with advanced non-small cell lung cancer and head and neck cancer. The findings were considered to reflect the physiological conditions present at the time of radiotherapy and these were related to acute normal tissue reactions and tumour control. Although 53% of the patients showed some impairment of lung function and 47% demonstrated a haemoglobin oxygen saturation below the normal range, oxygen partial pressure was below expected levels in fewer patients (27%) and total arterial oxygen content was below normal in only 12% of patients. No correlation was found between the tests performed and the severity of acute morbidity or with local tumour control. In the patients with carcinoma of the bronchus, there was a trend for incomplete tumour control to be associated with a lower haemoglobin level, but this did not reach statistical significance. In patients selected for curative radiotherapy, lung function would not appear to be an important factor influencing the response of normal tissues or tumour to irradiation.

Adult

Continuous, hyperfractionated, accelerated radiotherapy (CHART) in non-small cell carcinoma of the bronchus.

Between January 1985 and December 1988, 62 patients with locally advanced carcinoma of the bronchus were treated by radiotherapy using continuous, hyperfractionated, accelerated radiotherapy (CHART). With this regime on each of 12 consecutive days 3 fractions were given with a time interval of 6 hr between each. Initially a dose fraction of 1.4 Gy was used and a total of 50.4 Gy was achieved in 23 patients. As tolerance was good, the dose increment was raised to 1.5 Gy and the total to 54 Gy in the subsequent 39 patients. Esophagitis was the only immediate complication, and although most patients were reduced to a fluid diet for a period, recovery was complete and only one patient required endo-esophageal tube feeding for a short time. The results observed so far have been assessed against those in a previous trial of a radiosensitizer in cases similarly accepted for treatment. Complete regression, as observed radiologically, was achieved by 42%; this can be compared with 15% of the previously treated series. At 1 year the survival probability was 64% compared with a previous 44% and at 2 years 34% compared with a previous 12%. A randomized controlled clinical trial is now planned.

Carcinoma, Bronchogenic

The rationale for continuous, hyperfractionated, accelerated radiotherapy (CHART).

Continuous, hyperfractionated, accelerated radiotherapy (CHART) was devised to give the maximum chance of improving clinical radiotherapy and was based upon available radiobiological evidence. A pilot study, begun in 1985, has now included 210 patients. When comparison is made with previously treated cases, improved results have been seen in the two main groups included, that is, advanced head and neck and bronchial carcinomas. Multi-center randomized controlled clinical trials are planned.

Humans

An audit of head and neck cancer treatment in a Regional Centre for Radiotherapy and Oncology.

All patients with head and neck cancer attending the Regional Centre for Radiotherapy and Oncology at Mount Vernon hospital during the 8-year period from 1 January 1980 to 31 December 1987 have been included in this review. The 545 patients presenting a new primary carcinoma without evidence for metastasis outside the locoregional area, who were treated primarily by radiotherapy are the subject of this present audit. The characteristics of the patients, of the tumours and of the treatment given have been related to outcome. Early tumours (T1 and T2 which were node-negative) showed a complete response (CR) rate of 94% whereas more advanced tumours (T1 and T2 with palpable lymph nodes) showed a CR of 59%. The probability of local tumour control at 5 years was 77% in those without nodes and 20% in those with nodes. For more advanced disease (T3 and T4 tumours), initial CR was 72% in node-negative disease and 32% when the nodes were positive. At 5 years, the probability of local tumour control fell to 37% and 0 respectively. CR, freedom from recurrence and survival were statistically significantly related to T stage, N stage and site of primary tumour. The results compare favourably with those reported by other institutions. The development of medical audit and its influence on treatment policy are considered.

Adolescent

Smoking and mucosal reactions to radiotherapy.

The pattern of cigarette smoking of 41 patients receiving continuous, hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer was examined to determine any relationship with the duration of mucositis. The uniformity of the treatment given made it possible to perform an analysis of the factors influencing the duration of the mucositis. There was no correlation with age, sex or weight loss prior to treatment. A highly significant correlation was shown with smoking during and/or after treatment (p = 0.014) and with the volume of mucosa irradiated (p = 0.025). Both appeared to act independently. It is important to encourage patients to cease smoking totally, prior to radiotherapy, to minimize the duration of mucositis associated with radiotherapy.

Adolescent

The recording of morbidity related to radiotherapy.

Radiation morbidity is as important as tumour control when determining the value of radiotherapy, but there is no internationally agreed system for the recording of morbidity. A scheme based upon the scoring of the elements which make up morbidity has been endorsed by a 2-day Workshop sponsored by the Medical Research Council and a system is now available for trial.

Digestive System

Continuous hyperfractionated accelerated radiotherapy in locally advanced carcinoma of the head and neck region.

Shortening of the overall duration of radiotherapy would reduce the possibility repopulation of tumor during treatment. Most clinical trials of such accelerated radiotherapy have incorporated a split course to improve normal tissue tolerance. Any interruption, however, even for the week-end, may allow repopulation to occur. A scheme of radiotherapy has been used during which treatment was given 3 times per day on each of 12 consecutive days without interruption for the week-end. In a pilot study a significant improvement in survival and local tumor control has been achieved in 48 patients with head and neck tumors when comparison was made with a previously treated group. A randomized controlled clinical trial is planned.

Adult

Keynote address: hypoxic cell sensitizers: clinical developments.

"Tumours having small islands of cells should be radiosensitive, and those having large masses, radioresistant. This was found to be the case and there is a ready explanation for this: the outside cells are close to blood vessels and will thus be well supplied with oxygen, whilst the inside cells are not well placed in this respect. Now it is known that cells well supplied with oxygen are radiosensitive, compared to the same cells deprived of oxygen; it is therefore likely that for this reason, variation in blood supply, that the outside cells are more easily destroyed than those within."

Clinical Trials as Topic

The uptake of the radiosensitizing compound Ro 03-8799 (Pimonidazole) in human tumors.

The nitroimidazole, Ro 03-8799, has proved unique among the drugs tested as chemical hypoxic cell radiosensitizers because of the preferential concentration which has been observed in tumors. Our accumulation of experience has allowed new analyses to be performed upon 127 samples from 39 patients; 47 samples of normal tissue were also obtained from 26 of these patients. Tissue sampling was performed usually between 20 and 30 minutes after initiation of infusion of Ro 03-8799. By expressing results as tumor: plasma ratios, difficulties in comparison because of differing doses and body sizes, together with a variation in the actual time of sampling, have been avoided. A small portion of each specimen which was analyzed for drug concentration was also examined histologically to give an impression of the percentage of the specimen occupied by tumor cells. Analyses have shown that the average tumor concentration is approximately twice that of normal tissues which have been sampled and four times that in plasma. In 38 breast tumor samples, the concentration of drug varied directly as the proportion occupied by tumor cells. The highest tumor: plasma ratios were seen in samples taken from some samples of malignant melanoma. These findings confirm that a greater potency can be expected for this drug as a radiosensitizer because of its ability to enter tumor cells in high concentration. In drug development programs for chemical sensitizing and cytotoxic agents, drugs which show this phenomenon should be explored.

Breast Neoplasms

Normobaric oxygen as a sensitizer of hypoxic tumor cells.

A series of experiments have been performed to determine the relative radiosensitivities of a mouse mammary tumor (CA NT) irradiated in 100% normobaric oxygen or in air, using clinically relevant dose-fractionation schedules. The results demonstrate that normobaric oxygen is a potent radiosensitizer, its effect being more marked with smaller size fractions. Enhancement ratios (ER) of 1.23 to 1.45 were obtained. By contrast, no significant benefit was seen with single doses (ER = 1.05 +/- 0.14). The degree of radiosensitization with oxygen, in these fractionated regimens, is greater than that reported for the chemical radiosensitizer, misonidazole. It therefore seems appropriate to re-examine the clinical potential of normobaric oxygen and to consider how the conditions of normobaric radiotherapy achieved in the laboratory can be translated to man.

Adenocarcinoma

c-myc oncogene expression and clinical outcome in carcinoma of the cervix.

The expression of the c-myc oncogene was studied in paraffin-embedded specimens of cervical biopsies using a monoclonal antibody which binds to the 62,000 Dalton protein encoded by the c-myc gene. A range of cervical cancers from intraepithelial neoplasia to advanced grade IV tumours were studied together with normal cervical biopsies; c-myc status was correlated to clinical progress. There was no correlation seen between the clinical stage of the disease at presentation and c-myc expression. The 15 patients with c-myc negative cervical cancers were shown to have better disease free (mean--95.4 mos) and total survival (mean 118.0--mos) compared to the 16 patients that were c-myc positive 28.4 and 48.4 mos respectively). The pattern of recurrence differed between the two groups with c-myc positive tumours more likely to develop extra pelvic metastatic disease. The c-myc status of cervical cancer offers a prognostic indicator that could be useful in guiding treatment decisions.

Female