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H R Withers

Publications and source records attributed to H R Withers.

At least 127 records · Page 7Linked to original sources
PubMed1984

Biological bases for modifying conventional fractionation regimens in radiotherapy.

Radiobiological data concerning dose fractionation that have mostly become available only during the past decade could be used to design modifications of conventional radiotherapy that may be necessary in developing countries. Such modifications made in the past without the benefit of recent advances in radiobiological understanding have been disastrous (e.g. [23]). Since it is unreasonable to expect developing countries to support radiobiology research when there are more pressing priorities for their national resources, their interests could be best served by making available to them, through some agency such as the World Health Organization, the consultative services of radiotherapists and radiobiologists to resolve specific problems and thereby to help them achieve maximum cost-effectiveness in the utilization of their available radiotherapy facilities.

Animals↗
PubMed1984

Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair.

A model is proposed to account for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing numbers of ever-smaller fractional doses, the model transforms into the accumulation model (Roesch, 1978) of survival after continuous irradiation. When it is adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is some advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since in addition to determination of repair capacity (defined by beta/alpha) there is an estimate of repair kinetics (defined by the halftime T1/2 for repair of sublethal injury). There is a saving in overall treatment time with either method, thereby reducing the influence of regeneration on the interpretation of the results. The results of analyses of previously published data are presented to illustrate the use of the models. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of beta/alpha were approximately 0.1 Gy-1. From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and beta/alpha was 0.27 Gy-1. In the rat spinal cord beta/alpha was 0.7 Gy-1 and T 1/2 was 1.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Can late effects of neutron irradiation in man be estimated from early responses?

Slowly-developing tissue changes after neutron irradiation should be more easily predicted from acutely-developing injury than is the case with X rays. The difference between tissue responses to neutrons and X rays is that cell survival in both rapidly and slowly responding tissues is a direct logarithmic function of neutron dose, at least up to about 3 Gy, whereas the X-ray dose-survival relationship differs between the two types of tissue: the target cells for late injury are more susceptible to killing from accumulation of sub-lethal X-ray injury and hence the survival curve diverges from its initial essentially linear region more rapidly than does that for the target cells for acute injury.

Animals↗
PubMed1983

A dose-surviving fraction curve for mouse colonic mucosa.

A dose-surviving fraction curve representing the response of the mouse colonic mucosa to single doses of 137Cs gamma radiation was obtained from the results of a multifraction in vivo colony assay. Construction of the curve required an estimate of the average number of clonogens initially present per colonic crypt. The estimated clonogen count (88) was determined by a statistical method based on the use of doses per fraction common to different fractionation protocols. Parameters for the LQ and TC models of cell survival were obtained by weighted least-squares fits to the data. A comparison of the survival characteristics of cells from the mouse colonic and jejunal crypts suggested that the epithelium of the colon is less radiosensitive than that of the jejunum.

Animals↗
PubMed1983

Accelerated fractionation vs hyperfractionation: rationales for several treatments per day.

Treatment with several doses per day offers the prospect of a significant therapeutic gain using readily available low LET beams. These regimens can be classified as either accelerated fractionation or hyperfractionation according to their rationales. With accelerated fractionation a conventional number of dose fractions is delivered in a significantly shortened overall treatment time in order to reduce the opportunity for tumor cell regeneration during treatment. With hyperfractionation, on the other hand, a large number of significantly reduced dose fractions is used to give a greater total dose in a conventional overall treatment time. The rationale for this strategy is threefold: 1) increased opportunity for tumor cell redistribution and reoxygenation between dose fractions: 2) a possibly lower oxygen enhancement ratio with small incremental doses; and 3) different sparing of late reacting normal tissues with small dose fractions. A review of the published clinical experience with multiple fractions per day treatment reveals few studies of either pure accelerated fractionation or hyperfractionation since both are limited by acute normal tissue reactions. This has led to a variety of hybrid regimens, some of which have no clear rationale. The choice between accelerated fractionation and hyperfractionation is determined by the regenerative capability of tumor clonogens during treatment. A method of selection based on potential doubling times is presented.

Clone Cells↗
PubMed1983

A new isoeffect curve for change in dose per fraction.

A method is proposed for using survival curve parameters for calculating the change in total dose necessary to achieve an equal response in a tissue when the dose per fraction is varied. The method uses the ratio alpha/beta of the coefficients of the linear quadratic survival formula and accounts only for the effect of repair of cellular injury. Absolute values for alpha and beta are not required. The isoeffect curves vary for different tissues. A dose adjustment to account for differences in the regeneration of surviving cells that might result from changing a treatment regimen must be made separately and will also vary from tissue to tissue. Examples of the use of the curves are given. At present, the curves, particularly those for late effects, are uncertain and caution should be observed in using them until they are defined more accurately with additional data.

Cell Survival↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

Biological bases for high RBE values for late effects of neutron irradiation.

The late effects of fractionated irradiation with neutrons have been relatively more severe than after x-irradiation. Reasons for the RBEn/x being higher for late than for acute effects may include: (1) Late effects are reduced more by fractionation of X ray doses than are acute effects, whereas, with neutrons, the fractionation response is the same in rapidly-and slowly-responding tissues; (2) Late-responding tissues are less "sensitized" (and are, therefore, relatively protected) by redistribution throughout the division cycle during a fractionated regimen than are acutely-responding tissues: since neutron responses are less affected by cell-cycle distribution than are X ray responses, the relative protection of slowly-responding tissues is less; (3) The target cells for late, but not acute injury, may repair potentially lethal damage after X ray, but not after neutron exposure. Thus, the dissociation of RBE values for acute and late injury reflects mainly the dissociation between acute and late responses to conventional fractionated X ray regimens and, from the point of view of complications of radiotherapy, we should not condemn neutrons but praise X rays. Since fractionation of neutron doses into increments equivalent to those used in X ray therapy does not provide a preferential sparing of slowly-responding tissues, it is reasonable to shorten the overall duration of neutron treatment to deliver the total dose tolerated by the relevant "late-effects" tissue(s) in the shortest time consistent with acceptable acute responses.

Animals↗
PubMed1982

50-MEVd leads to Be neutrons: a comparison of normal tissue tolerance in animals with clinical observations in patients.

The acute and late effects of 50 MeV neutrons were investigated by irradiating a variety of organ systems in large animals using dosage schedules similar to those that have been employed clinically. The RBEs for acute effects in pig skin and rhesus monkey oral mucosa were significantly less than the RBEs for late effects. This observation has also been noticed clinically. The RBEs for late effects in pig skin, rhesus monkey oral mucosa, and rhesus monkey kidney were consistent with values of 3.1 to 3.4 relative to approximately 200 rad 60Co fractions and approximately 2.2 to 2.6 relative to approximately 400 rad 60Co fractions. The RBE for radiation myelitis was significantly greater (4.2 to 4.6 relative to approximately 270 rad 60Co fractions). The tolerance doses for 50 MeVd leads to Be neutrons in large animals were approximately 2200 radn gamma/61/2 weeks for skin contraction, approximately 2100 radn gamma/61/2 weeks for oromucosal necrosis, approximately 1300 radn gamma/41/2 weeks for radiation myelitis, and approximately 960 radn gamma/4 weeks for radiation nephritis. These values correlate well with clinical observations at TAMVEC, since the majority of soft tissue complications in patients occurred following tissue doses in excess of 2100 radn gamma.

Animals↗
PubMed1982

The use of irradiation therapy in the treatment of tumors of the rectum and rectosigmoid.

As a means of increasing local control and disease-free survival in patients with carcinoma of the rectum and rectosigmoid, preoperative and postoperative irradiation therapy have been shown to be effective. The question of the sequence of delivering adjuvant radiation therapy is not settled; however, the benefits and deficits of irradiation therapy as an adjuvant to surgery preoperative or post-operative are reviewed. Basic principles of radiation oncology affecting the selection of the sequence and technique of treatment are discussed.

Female↗
PubMed1981

Long-term effects of pulmonary damage in mice on lung weight, compliance, hydroxyproline content and formation of metastases.

The development of "metastatic" colonies of fibrosarcoma in the lungs of mice after IV injection of a single-cell suspension of tumour cells varied with time after irradiation or administration of bleomycin. Most notably, there was a late radiation-induced enhancement of colony-forming efficiency that coincided with an increase in lung weight and hydroxyproline content and a decrease in compliance. There was no radiation-induced enhancement of "spontaneous" metastases from a mammary carcinoma implanted in the thighs of the animal. The sequence of events after administration of bleomycin was similar to that after irradiation, but the duration of the treatment was different and the temporal relationship between enhanced colony-forming efficiency and changes in lung weight and hydroxyproline content was not as clear cut.

Animals↗