A heterogeneous dose distribution in simultaneous integrated boost: the role of the clonogenic cell density on the tumor control probability

Strigari, Lidia; D’Andrea, M.; Abate, A; Benassi, Marcello

doi:10.1088/0031-9155/53/19/001

Cited by 17 publications

(11 citation statements)

References 39 publications

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“…is the fraction of cells obtained from gaussian distributions of ln (N i ) values, with a mean value of ln(N 0 ) and an SD of s ln(N) (17). A modified formalism of the NTCP model for the treatment of HCC, based on the Lyman-Burman Kutcher model, was used to evaluate specific radiobiologic parameters.…”

Section: Radiobiologic Modelsmentioning

confidence: 99%

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations

Strigari¹,

Sciuto²,

Rea³

et al. 2010

J Nucl Med

224

187

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Radioactive 90 Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normaltissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. Methods: Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of 99m Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the 90 Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. Results: Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the $grade 2 (G2), $grade 3 (G3), and $grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the $G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n 5 1. Conclusion: The radiobiologic approach, based on patient-specific dosimetry, could improve the 90 Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.

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Section: Radiobiologic Modelsmentioning

confidence: 99%

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations

Strigari¹,

Sciuto²,

Rea³

et al. 2010

J Nucl Med

224

187

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“…The treatment setup was generally based on a seven-field setup using 6-MV photon beams and a simultaneous integrated boost (SIB) technique (29).…”

Section: Patient Populationmentioning

confidence: 99%

A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

Strigari

Benassi

Arcangeli

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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“…Therefore, the historical inability to distinguish among effects resulting in differences in radiosensitivity could be overcome through new knowledge concerning heterogeneity [26,27]. These effects are well known from preclinical studies, and could be used to reduce uncertainties and investigated through clinical trials [28].…”

Section: Discussionmentioning

confidence: 99%

Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

Pedicini

Caivano

Jereczek-Fossa

et al. 2012

Theor Biol Med Model

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PurposeTo estimate the effects of heterogeneity on tumour cell sensitivity to radiotherapy combined with radiosensitizing agents attributable to differences in expression levels of Epidermal Growth Factor Receptor (EGFr).Materials and methodsDifferences in radiosensitivity are not limited to cells of different cancer histotypes but also occur within the same cancer, or appear during radiotherapy if radiosensitizing drugs are combined with ionizing radiation. A modified biologically effective dose (MBED), has been introduced to account for changes in radiosensitivity parameters (α and α/β) rather than changes in dose/fraction or total dose as normally done with standard biologically effective dose (BED). The MBED approach was applied to cases of EGFr over-expression and cases where EGFr inhibitors were combined with radiation. Representative examples in clinical practice were considered.ResultsAssuming membrane EGFr over-expression corresponds to reduced radiosensitivity (αH = 0.15 Gy-1 and αH/βH = 7.5 Gy) relative to normal radiosensitivity (α = 0.2 Gy-1 and α/β = 10 Gy), an increased dose per fraction of 2.42 Gy was obtained through the application of MBED, which is equivalent to the effect of a reference schedule with 30 fractions of 2 Gy. An equivalent hypo-fractionated regime with a dose per fraction of 2.80 Gy is obtained if 25 fractions are set. Dose fractionations modulated according to drug pharmacokinetics are estimated for combined treatments with biological drugs. Soft and strong modulated equivalent hypo-fractionations result from subtraction of 5 or 10 fractions, respectively.ConclusionsDuring this computational study, a new radiobiological tool has been introduced. The MBED allows the required dose per fraction to be estimated when tumour radiosensitivity is reduced because EGFr is over-expressed. If radiotherapy treatment is combined with EGFr inhibitors, MBED suggests new treatment strategies, with schedules modulated according to drug pharmacokinetics.

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A heterogeneous dose distribution in simultaneous integrated boost: the role of the clonogenic cell density on the tumor control probability

Cited by 17 publications

References 39 publications

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations

A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

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A heterogeneous dose distribution in simultaneous integrated boost: the role of the clonogenic cell density on the tumor control probability

Cited by 17 publications

References 39 publications

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations

A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

Modelling the correlation between EGFr expression and tumour cell radiosensitivity, and combined treatments of radiation and monoclonal antibody EGFr inhibitors

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Product

Resources

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Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations

Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with ⁹⁰Y-SIR Spheres: Radiobiologic Considerations