The use of the linear quadratic model in radiotherapy: a review

Jones, L. E.; Hoban, Peter; Metcalfe, Peter E

doi:10.1007/bf03178355

Cited by 62 publications

(51 citation statements)

References 120 publications

(36 reference statements)

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“…The impact of all these variables is demonstrated in the calculation of the biological effective dose of irradiation (BED) using the linear quadratic model [2,14]. The use of BED makes it possible to quantify the biological effects of different radiation schedules and, thus, providing a homogenous method of comparing their impact on hypothalamic and/or pituitary function [15].…”

Section: Radiobiologymentioning

confidence: 99%

Hypopituitarism As a Consequence of Brain Tumours and Radiotherapy

Darzy

Shalet

2005

Pituitary

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Radiation-induced damage to the hypothalamic-pituitary (h-p) axis is associated with a wide spectrum of subtle and frank abnormalities in anterior pituitary hormones secretion. The frequency, rapidity of onset and the severity of these abnormalities correlate with the total radiation dose delivered to the h-p axis, as well as the fraction size, younger age at irradiation, prior pituitary compromise by tumour and/or surgery and the length of follow up. Whilst, the hypothalamus is the primary site of radiation-induced damage, secondary pituitary atrophy evolves with time due to impaired secretion of hypothalamic trophic factors and/or time-dependent direct radiation-induced damage. Selective radiosensitivity in the neuroendocrine axes with the GH axis being the most vulnerable to radiation damage accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h-p axis with doses less than 30 Gy. With higher radiation doses (30-50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50-100%, and TSH and ACTH deficiency start to occur with a long-term cumulative frequency of 3-6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30-50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30-60% after 10 years) occur after more intensive irradiation (>70 Gy) used for nasopharyngeal carcinomas and tumours of the skull base and following conventional irradiation (30-50 Gy) for pituitary tumours. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy to improve linear growth and prevent short stature in children cured from cancer, and in adults preserve sexual function, prevent ill health and osteoporosis and improve the quality of life.

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Section: Radiobiologymentioning

confidence: 99%

Hypopituitarism As a Consequence of Brain Tumours and Radiotherapy

Darzy

Shalet

2005

Pituitary

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“…is still capable of originating a clone). The quadratic term βd 2 represents "two-track action" where damage from two different radiation tracks interacts to inactivate the cell; the linear term αd represents onetrack inactivation [reviewed in (Guerrero et al, 2002;Jones et al, 2001;Sachs and Brenner, 1998;Sachs et al, 1997)]. In most environmental or occupational risk estimation situations, the relevant doses are so low that exp(-αd-βd 2 )=1 to good approximation, but for second cancer scenarios such is by no means the case.…”

Section: Err = Abmentioning

confidence: 99%

Second cancers after fractionated radiotherapy: Stochastic population dynamics effects

Sachs

Shuryak

Brenner

et al. 2007

Journal of Theoretical Biology

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When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well characterized doses of a well studied carcinogen, followed by long-term monitoring.In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze if radiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this IIP model. Combining Monte Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance ≫ mean, even when pre-malignant clones are Poisson-distributed. Thus fewer patients would be affected, but with a higher probability, than a deterministic model, tracking average pre-malignant cell numbers, would predict. Our results are applied to data on breast cancers after radiotherapy for Hodgkin disease. The stochastic IIP analysis, unlike the deterministic one, indicates: a) initiated, pre-malignant cells can have a growth advantage during repopulation, not just during the longer tumor latency period that follows; b) weekend treatment gaps during radiotherapy, apart from decreasing the probability of eradicating the primary cancer, substantially increase the risk of later second cancers.

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“…Kron provided two detailed articles on thermoluminescence dosimetry and its applications in medicine that describes the history, physics materials, equipment and clinical applications for this dosimetric technique 82,83 . Holloway (nee Jones), Hoban and Metcalfe combined to provide a review of the linear quadratic model and volume irradiated when considering radiobiological effects 84,85 . Both these papers provide very good information for the novice.…”

Section: Invited Review Papersmentioning

confidence: 99%

Thirty year celebration of journal publications on radiation oncology medical physics

Oliver

2007

Australas. Phys. Eng. Sci. Med.

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The Australasian Physical & Engineering Sciences in Medicine Journal (APESM) is an avenue for the profession to report scientific work in medicine; provide a facility for the publication of current work, new research and new techniques developed or reviewed; report on professional news from elsewhere and; publish the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) policies and protocols. The journal is a vital instrument within the ACPSEM organisation with a worldwide circulation. This review of APESM on medical physics in radiation oncology is meant to be a progress summary of work in that specialty. Even so, it has become a lengthy appraisal due to the many years involved. In considering publications related to medical physics in radiation oncology, this review has shown the progression of the College journal to an international journal. There is an increase in the number of papers contributed from Asia and other countries world wide for this discipline. Growth in the number of contributions should continue to rise. In order to provide some appreciation of where the present medical physics activity arose from, this article commences its discussion in 1959 and progresses towards the present, describing along the way, from radiation oncology papers published in APESM, the use of linear accelerators, brachytherapy, the medical physics workforce, the formation of the ACPSEM, and the more modern developments in radiotherapy such as 3-D treatment planning and IMRT.

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The use of the linear quadratic model in radiotherapy: a review

Cited by 62 publications

References 120 publications

Hypopituitarism As a Consequence of Brain Tumours and Radiotherapy

Hypopituitarism As a Consequence of Brain Tumours and Radiotherapy

Second cancers after fractionated radiotherapy: Stochastic population dynamics effects

Thirty year celebration of journal publications on radiation oncology medical physics

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