The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies

Leeuwen, Caspar M. van; Oei, Arlene L.; Crezee, J.; Bel, Arjan; Franken, Nicolaas A.P.; Stalpers, Lukas J.A.; Kok, H. Petra

doi:10.1186/s13014-018-1040-z

Cited by 371 publications

(327 citation statements)

References 84 publications

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“…The MK model of Hawkins, the most recent version of the LEM, and the RMF model are examples of mechanism‐inspired models that link the RBE for reproductive cell survival to the induction and biological processing of sublethal damage, especially the DNA DSB, into more lethal forms of damage, such as chromosome aberrations. The MK, LEM, and RMF models all aim to derive the biological effects of ion radiation from the response of cells or tissues to low LET photons, thus efficiently exploiting the large amount of in vitro and in vivo data in the literature . All three models provide quantitative frameworks to estimate trends in the LQ model radiation sensitivity parameters α, β (or α/β) as a function of linear energy transfer (LET), lineal energy ( y ), or other metrics of radiation quality, such as the square of the ratio of the effective charge of the ion ( Z eff ) divided by the speed of the ion relative to the speed of light (β).…”

Section: Rbe Models and Mechanisms Of Actionmentioning

confidence: 99%

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A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

et al. 2018

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Background and Significance The application of heavy ion beams in cancer therapy must account for the increasing relative biological effectiveness (RBE) with increasing penetration depth when determining dose prescriptions and organ at risk (OAR) constraints in treatment planning. Because RBE depends in a complex manner on factors such as the ion type, energy, cell and tissue radiosensitivity, physical dose, biological endpoint, and position within and outside treatment fields, biophysical models reflecting these dependencies are required for the personalization and optimization of treatment plans. Aim To review and compare three mechanism‐inspired models which predict the complexities of particle RBE for various ion types, energies, linear energy transfer (LET) values and tissue radiation sensitivities. Methods The review of models and mechanisms focuses on the Local Effect Model (LEM), the Microdosimetric‐Kinetic (MK) model, and the Repair‐Misrepair‐Fixation (RMF) model in combination with the Monte Carlo Damage Simulation (MCDS). These models relate the induction of potentially lethal double strand breaks (DSBs) to the subsequent interactions and biological processing of DSB into more lethal forms of damage. A key element to explain the increased biological effectiveness of high LET ions compared to MV x rays is the characterization of the number and local complexity (clustering) of the initial DSB produced within a cell. For high LET ions, the spatial density of DSB induction along an ion's trajectory is much greater than along the path of a low LET electron, such as the secondary electrons produced by the megavoltage (MV) x rays used in conventional radiation therapy. The main aspects of the three models are introduced and the conceptual similarities and differences are critiqued and highlighted. Model predictions are compared in terms of the RBE for DSB induction and for reproductive cell survival. Results and Conclusions Comparisons of the RBE for DSB induction and for cell survival are presented for proton (1H), helium (4He), and carbon (12C) ions for the therapeutically most relevant range of ion beam energies. The reviewed models embody mechanisms of action acting over the spatial scales underlying the biological processing of potentially lethal DSB into more lethal forms of damage. Differences among the number and types of input parameters, relevant biological targets, and the computational approaches among the LEM, MK and RMF models are summarized and critiqued. Potential experiments to test some of the seemingly contradictory aspects of the models are discussed.

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Section: Rbe Models and Mechanisms Of Actionmentioning

confidence: 99%

“…Values of (α/β) R for an array of normal tissue and malignant cell populations have been measured and tabulated . Because of the limited range of values of the domain diameter, RBE 1 can be estimated with some degree of confidence from Eq.…”

Section: Rbe Models and Mechanisms Of Actionmentioning

confidence: 99%

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

et al. 2018

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“…Paramètres radiobiologiques pour les cancers des voies aérodigestives supérieures [3,8]  pour les tissus sains à réponse tardive : α/β = 3 Gy ;…”

Section: Cancers Des Voies Aérodigestives Supérieuresunclassified

“…Les paramètres radiobiologiques pour les cancers du poumon non à petites cellules ont été publiés [5,8]. L'impact de l'étalement dans les cancers bronchiques a été clairement mis en évidence en cas de radiothérapie exclusive, mais aussi dans le cadre des associations de chimioradiothérapie concomitante [9,10].…”

Section: Cancer Du Poumon Non à Petites Cellulesunclassified

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Compensation de la dose totale en cas d’interruption temporaire de radiothérapie externe dans le contexte de la pandémie de COVID-19 : mise au point pratique

Azria

Hennequin

Giraud

2020

Cancer/Radiothérapie

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L'étalement est un facteur important de récidive locale et indirectement d'évolution à distance, notamment en cas de durée de traitement allongée. La pandémie actuelle a un impact sur les patients en cours de radiothérapie qui doivent interrompre leur traitement de manière parfois prolongée du fait de la nécessité de soins respiratoires induits par le COVID-19. Les modèles utilisés de compensation de la dose totale en cas d'interruption prolongée de la radiothérapie sont connus, mais il nous a semblé important de synthétiser afin que chaque oncologue radiothérapeute puisse proposer un traitement le plus optimal possible tant en termes de risque de récidive locale que de protection des tissus sains. L'objectif de ce type de recommandation est d'homogénéiser les pratiques de l'ensemble de la discipline. AbstractOverall treatment time is an important factor of local recurrence and indirectly of distant evolution, namely in case of protracted treatments. The current pandemic impacts on the duration of radiotherapy if patients under treatments and synchronously suffering from COVID-19. The models used to compensate the total dose in case of temporary treatment interruption are well known but it temps, en rapport avec la capacité de la tumeur à se diviser. Une majoration de la dose totale devient alors nécessaire afin de compenser cette repopulation tumorale.En pratique, si une interruption d'une durée « t » est survenue dans l'intervalle de temps initialement prévu de traitement « T », la durée d'allongement du traitement sera exactement de durée « t » mais avec une dose de compensation supérieure à la dose totale initialement prévue, à condition de contrôler la tolérance sur les tissus sains environnants.Cette notion d'« extra-dose » est nécessaire car le traitement est souvent repris dans la période de repopulation avec une iso-TCP50 nécessairement supérieure. Cela est valable si le fractionnement classique est maintenu et que la reprise de la radiothérapie n'inclut pas de séance le week-end et/ou n'utilise pas un hyperfractionnement quotidien.

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Association of Radiation and Procarbazine Dose With Risk of Colorectal Cancer Among Survivors of Hodgkin Lymphoma

et al. 2023

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ImportanceHodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.ObjectiveTo quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.Design, Setting, and ParticipantsA nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.ExposuresMean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.Main Outcomes and MeasuresExcess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.ResultsThe study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.Conclusions and RelevanceThis nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.

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The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies

Cited by 371 publications

References 84 publications

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)

Compensation de la dose totale en cas d’interruption temporaire de radiothérapie externe dans le contexte de la pandémie de COVID-19 : mise au point pratique

Association of Radiation and Procarbazine Dose With Risk of Colorectal Cancer Among Survivors of Hodgkin Lymphoma

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