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Biomedical subjects

G H Fletcher

Publications and source records attributed to G H Fletcher.

At least 73 records · Page 4Linked to original sources

Tumor radioresistance in clinical radiotherapy.

Tumor radioresistance in clinical radiotherapy implies failure to achieve loco-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be a result of many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose response relationships for human cancers suggest that in many sites, tumors are heterogenous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trails of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to predictively identify its cause in the individual patient.

Cell Line↗

Anatomical coverage in elective irradiation of the neck for squamous cell carcinoma of the oral tongue.

From January 1954 through December 1978, 146 patients with squamous cell carcinoma of the oral tongue and clinically negative neck had their primary lesion controlled with irradiation. Metastases to the neck developed later in: 27 of 76 patients (36%) treated by interstitial implantation; nine of 27 patients (33%) who received 2,000 rad in five fractions to the upper neck prior to the implant; eight of 19 (42%) patients who received 5,000 rad through an upper ipsilateral neck field prior to the implant; four of 24 patients (16.6%) who received 5,000 rad through bilateral portals to the upper neck with or without irradiation of the lower neck. In the 43 ipsilateral neck failures, 23 were in the upper jugular chain, (posterior subdigastric nodes), 12 in the mid-jugular, three in the lower jugular, and four in the more anterior part of the subdigastric area. There was one failure in the posterior cervical chain, and five contralateral neck failures. A review of the treatment charts showed that the patients who had an ipsilateral upper neck field only, had smaller portals because the irradiation was tailored to produce shrinkage of the primary tumor prior to needling. To include adequate coverage of the posterior subdigastric nodes (upper jugular), the bodies of the vertebrae must be seen on the simulator films. Also the junction of the subdigastric and the mid-jugular lymphatics must be covered. Although there were only three failures in the lower jugular nodes, it is technically easier to treat the upper mid-jugular nodes through an anterior appositional portal to the lower neck. A dose of 5,000 rad must be given since 2,000 rad, even if delivered in five fractions, gives a failure rate as if there had been no irradiation to the neck.

Brachytherapy↗

Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships.

Clinical and experimental evidence for divergent changes in early and late radiation responses in normal tissues after changes in dose fractionation indicate a greater sensitivity of late responses to changes in dose per fraction. In experimental studies of the effect of dose per fraction on early and late isoeffects, a larger number-of-fractions exponent for the late responses is the rule. These findings imply that the shape of the dose-survival curve for the target cells whose depletion results in late effects is different from that for target cells for acute effects: as the dose increases the contribution to cell killing from accumulated sublethal injury, relative to killing from single hit events, increases more rapidly in the target cells for late effects. In other words, the survival curve for the target cells for late injury must be "curvier" than that for acute effects. Although such survival curve characteristics are independent of the survival curve model chosen to describe them, they would represent, in terms of the parameters of the linear quadratic model, S = e -alphaD-beta D2, a higher beta/alpha ratio for late effects. If the dose survival characteristics of tumor clonogens resemble those of the target cells in acutely responding normal tissues, and if late injury in normal tissues is dose-limiting, then a therapeutic gain would result from reducing the size of dose per fraction by hyperfractionation. Conversely, increasing the size of dose per fraction should reduce the therapeutic differential.

Dose-Response Relationship, Radiation↗

Squamous cell carcinoma of the pyriform sinus.

This is a review of 418 patients with cancer of the pyriform sinus who had complete treatment at University of Texas M. D. Anderson Hospital, treated over a 28-year time span. Treatment modalities used included radiation therapy, surgery, and planned combined treatment, primarily in the form of surgery and postoperative radiation therapy. Superficial lesions, with no impairment of laryngeal motility, are suitable for irradiation therapy planned for cure. (The policies of treatment have changed throughout the years). Analysis is made comparing the results of the larger groups of patients treated by surgery only, or surgery followed by postoperative radiation therapy. There is a significant lower incidence of failure above the clavicle in the combined treatment group, and a better 5-year survival. Rate of recurrences and the specific sites of failure above the clavicles are discussed, as well as the means of preventing such. The causes of death between 2 and 5 years are presented.

Aged↗

Retreatment of recurrent nasopharyngeal carcinoma.

Thirty patients with recurrent primary nasopharyngeal carcinoma were reirradiated between 1949 and 1976. Twenty eventually demonstrated recurrence at or near the primary site, involving the nasopharynx in 4 and the central nervous system in 16. Long-term palliation was often achieved, and there were no severe complications except for one patient who died of necrosis of the base of the skull. The most frequent problems were hearing loss and trismus; necrosis of the nasopharynx was seen in only 2 patients. With therapy in the range of 18-25 MeV, significant palliation and an occasional cure can be achieved without excessive risk. Recurrent disease involving the skull may be controlled for several years using current techniques.

Carcinoma, Squamous Cell↗

The curative value of irradiation in the treatment of nondisseminated breast cancer.

Data are now available from two randomized trials showing that adjuvant irradiation of the internal mammary and supraclavicular nodes following a radical or modified radical mastectomy results in increased survival rates. A retrospective analysis of 1111 patients treated at M. D. Anderson Hospital with radical mastectomies with and without irradiation to the peripheral lymphatic areas shows equal ten-year survival rates in irradiated and unirradiated patients in spite of the fact that the irradiated patients had a much higher incidence of histologically positive nodes. There is a significant percentage of patients surviving ten-years in 353 patients with locally or regionally advanced tumors treated with simple mastectomy and irradiation without chemotherapy. Radiation of gross local and regional recurrences has a high risk of failure and radiation sequelae.

Breast Neoplasms↗