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Biomedical subjects

J F Fowler

Publications and source records attributed to J F Fowler.

At least 109 records · Page 6Linked to original sources
PubMed1992

Loss of local control with prolongation in radiotherapy.

Twelve published clinical results of radical radiotherapy of head and neck cancer have been reviewed, seven of them with fresh multivariate analyses, to determine the magnitude of time factors relating local control to overall time. In all but two of the data sets a significant loss of local control was observed with prolongation. The median rate of loss was 14% in only 1 week, the range 3 to 25%. This corresponds to a median loss of 26% in 2 weeks (5-42%). These results are comparable with other, less detailed information. Whether these significant losses are due to proliferation of tumor cells or to other causes such as physician selection, it is clear that modest prolongation is associated with a lower chance of local control.

Head and Neck Neoplasms↗
PubMed1992

Salvage surgery following irradiation with different fractionation regimes in the treatment of carcinoma of the laryngo pharynx: experience gained from a British Institute of Radiology study.

The 10-year follow-up of patients in a clinical trial involving the comparison of treatment by three fractions per week versus five fractions per week in radiotherapy of squamous carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. No statistically significant differences have been found between the two trial arms in terms of overall survival, age corrected survival, local recurrence, laryngectomy-free rates or effects on the normal tissues. Local recurrence was found in 320 of the 713 evaluable patients (45 per cent). Salvage laryngectomy was performed in 151 of the 320 patients with recurrence (47 per cent). Survival at 10 years for all node negative patients was 50 per cent in those patients without primary recurrence, compared with 40 per cent in those undergoing salvage laryngectomy.

Carcinoma, Squamous Cell↗
PubMed1992

Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. I. Radiosensitization of human colon cancer cells by iododeoxyuridine.

Radiosensitization by iododeoxyuridine (IdU) is a method of enhancing cell killing in the radiotherapy of human cancers, especially for tumors that proliferate faster than the surrounding normal tissues, such as might appear in brain or liver. We have investigated in vitro the relationship between the amount of thymidine replacement by IdU and the resulting radiosensitization in two human colon cancer cell lines, HCT 116 and HT 29, with differing inherent sensitivities to X rays. The results show that an increase in the initial slope of the cell survival curve was the predominant mode of radiosensitization. In this situation, the emphasis on changes in the initial slope suggest the use of a survival curve model that contains the initial slope as a defined variable, which the traditional single-hit, multitarget model does not. We present our analyses mainly in terms of alpha (initial slope) and changes in surviving fraction at 2 Gy and also as a modified form of sensitizer enhancement ratio that describes the dose-modifying factor of IdU at a single radiation dose of 2 Gy (SER 2 Gy). Iododeoxyuridine is an effective radiosensitizer in both cell lines, but IdU appears especially effective in increasing the initial slope of the more radioresistant line, the HT 29 cells.

Cell Survival↗
PubMed1992

Linear-quadratic analysis of radiosensitization by halogenated pyrimidines. II. Radiosensitization of human colon cancer cells by bromodeoxyuridine.

As a continuation of the studies in Part I (Miller, Fowler, and Kinsella, Radiat. Res. 131, 000-000, 1992), which examined the radiosensitizing effects of iododeoxyuridine (IdU), similar experiments with bromodeoxyuridine (BrdU) were conducted concurrently to characterize its effects on the shape of the radiation survival curves of cells of two human colon cancer cell lines, HT 29 and HCT 116. The efficiency of radiosensitization by BrdU, expressed as a function of percentage thymidine replacement, was lower when compared to IdU in both cell lines. However, the major radiosensitizing effect of BrdU was manifest as an increase in the initial slope (alpha), just as observed for IdU. However, with BrdU, in contrast to IdU, an increase in curvature (repairable damage) was also evident. Cells of the more radiosensitive line, HCT 116, showed less sensitization by either BrdU or IdU than cells of the more radioresistant line, HT 29. These results were consistent with the proposed mechanism of radiosensitization being an increase in the single-hit character of low-LET radiation. It follows that the radiosensitizing effects of both analogs were largest in the low-dose region of the survival curve.

Bromodeoxyuridine↗
PubMed1991

Keynote address: integration of cytostatic agents and radiation therapy: a different approach to "proliferating" human tumors.

Failure to achieve local and regional tumor control with radiation therapy remains a significant problem for a number of anatomic sites and can have a negative impact upon survival. There is emerging clinical and laboratory evidence that proliferation of tumor clonogens during the course of radiation treatment significantly impairs local control. Recent in situ studies suggest that as many as half of all human carcinomas have the potential to double their cell number in 5 or fewer days. Thus, cells that survive the initial treatments might rapidly repopulate a tumor, resulting in local failure. One potential clinical approach to reduce the impact of tumor cell repopulation during treatment would be to administer biological or chemical modifiers to slow or inhibit tumor proliferation. Examples of these cytostatic modifiers which are available for clinical testing now, or in the near future, include hormones, anti-hormones, growth factors, growth factor antagonists and other biologicals (e.g., interferons). Clinical alteration of the proliferative status of tumors could influence tumor control by reducing the impact of tumor cell proliferation during therapy, by modifying tumor cell radiosensitivity, or by favourably altering both. To appreciate the magnitude and the cumulative effect of these factors, newer technologies and experimental model systems need to be exploited in investigating correlations between proliferation and tumor control and between proliferative status and radiosensitivity. The design of future clinical trials using cytostatic agents and radiotherapy will rely heavily upon such basic information.

Antineoplastic Agents↗
PubMed1991

Apparent rates of proliferation of acutely responding normal tissues during radiotherapy of head and neck cancer.

Total doses, fraction sizes, and overall times reported to give "tolerance level" reactions in oral, pharyngeal, or laryngeal mucosa vary greatly in different countries. The variation in fraction size reviewed here is from 1.15 Gy (France) to 3.4 Gy (UK), and in overall time from 11 days (UK) through 3, 4, and 5 weeks (UK and Canada) to 7 weeks (USA and France). Using linear quadratic corrections for fraction size, and regression of the resulting "LQ doses" against overall time, it is found that the average rate of increase of dose for these normal tissue reactions is gamma/alpha = 63 to 69 cGy per day (along the initial slope of the underlying dose-response curve), which corresponds to 53 to 65 cGy per day when 2 Gy fractions are used. The range of uncertainty overlaps with that of estimated tumor proliferation rates in the head and neck by other authors, but there is no trend for these normal tissues to be proliferating consistently faster than tumors in the same sites. These conclusions must be interpreted with caution because of differences in acceptance of reaction level, treatment volume, and dose specification.

Cell Division↗
PubMed1991

Re-analysis of the time factor in local control by radiotherapy of T3T4 squamous cell carcinoma of the larynx.

The use of logistic regression for the analysis of local control data is illustrated via a re-analysis of previously published data. A larger effect of overall time is found than in the original publication. In addition, the original analysis of 50 percent effective dose (ED50) is found to have obscured the relationship between local control and overall time for some doses.

Carcinoma, Squamous Cell↗
PubMed1991

Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx.

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

Adult↗