Where Do We Look for Markers of Radiotherapy Fraction Size Sensitivity?

Somaiah, Navita; Rothkamm, Kai; Yarnold, John

doi:10.1016/j.clon.2015.06.006

Cited by 14 publications

(10 citation statements)

References 103 publications

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“…However, when including those cancers showing relatively high proliferation rates, there was no suggestion of a detriment using hypofractionated radiation therapy schedules giving 3 Gy per fraction. Other tumor types encompass wider ranges in proliferation and show higher average proliferation (7) . Our results should not be interpreted as demonstrating a general lack of association between proliferation and fraction sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Tissues with high proliferation indices, such as gastrointestinal mucosa and epidermis, are insensitive to fraction size. In contrast, late-reacting normal tissues, such as kidney, have low proliferative indices and are very sensitive to fraction size 7 , 8 . This study tests the hypothesis that the same association between proliferative indices and fractionation sensitivity in normal tissues extends to localized PCa.…”

Section: Introductionmentioning

confidence: 99%

“…The expectation is that highly proliferative cancers will show insensitivity to fraction size and be more likely to relapse after the reduced total dose in hypofractionated (>2 Gy) schedules. In contrast, slowly proliferating tumors are expected to be sensitive to fraction size, hence more likely to relapse after conventional fractionation (2 Gy) schedules (7) .…”

Section: Introductionmentioning

confidence: 99%

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Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer

Wilkins¹,

Gusterson

Szíjgyártó

et al. 2018

International Journal of Radiation Oncology*Biology*Physics

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PurposeTo assess whether the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiation therapy fractionation in patients with localized prostate tumors participating in a randomized trial of 3 radiation therapy fractionation schedules (74 Gy/37 fractions vs 60 Gy/20 fractions vs 57 Gy/19 fractions).Methods and MaterialsA matched case–control study design was used; patients with biochemical/clinical failure >2 years after radiation therapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, prostate-specific antigen, tumor stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker–fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.ResultsUsing 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (interquartile range, 3.9%-9.8%) and 11.0% (interquartile range, 7.0%-15.0%) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching variables and age, the odds of BCR were estimated to increase by 9% per 1% increase in mean Ki67 score (odds ratio 1.09; 95% confidence interval 1.04-1.15, P = .001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.ConclusionsDiagnostic Ki67 did not predict BCR according to fractionation schedule in CHHiP; however, it was a strong independent prognostic factor for BCR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer

Wilkins¹,

Gusterson

Szíjgyártó

et al. 2018

International Journal of Radiation Oncology*Biology*Physics

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“… 31 The radiobiological explanations for varying normal tissue and tumor responses to alterations in dose fractionation are an area of ongoing research. 32 …”

Section: Hypofractionated Rt Following Bcs Is Safe and Effectivementioning

confidence: 99%

Hypofractionated whole breast radiotherapy: current perspectives

Koulis¹,

Phan²,

Olivotto³

2015

BCTT

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Adjuvant radiotherapy (RT) is an important part of breast cancer management but the dose and fractionation schedules used are variable. A total of 50 Gy in 25 daily fractions delivered over 5 weeks is often considered the “standard” adjuvant RT prescription. Hypofractionated regimes such as 42.5 Gy in 16 daily fractions or 40 Gy in 15 daily fractions following breast-conserving surgery have proven to be equally effective and achieve similar or better cosmetic and normal tissue outcomes for both invasive and in situ diseases and when treating the regional nodes. Hypofractionation is more convenient for patients and less costly. However, certain patients at higher risk of RT late effects may benefit from a less intense, even more extended fractionation schedule. This review describes the indications for whole breast hypofractionated adjuvant RT for patients with breast cancer following breast-conserving surgery and proposes that hypofractionation should be the new “standard” for adjuvant breast cancer RT.

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“…2–4 Unlike tumor cells, normal cells repopulate during or shortly after a course of therapy, thus providing an opportunity for the repair of normal tissue damaged due to radiation. The difference in the shape of the radiation survival curve using various radiobiological models from clinical data helps to explain the clinical outcome from both dose size and fractionation scheme.…”

Section: Introductionmentioning

confidence: 99%

Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy

Makinde

Eke

Aryankalayil

et al. 2016

Seminars in Radiation Oncology

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The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy. We discuss the potential of using different radiation doses and MF adaptation for targeting transcription factors, immune and inflammatory response, and cell “stemness.” Given the complex genetic composition of tumors before treatment and their adaptation to drug treatment, innovative combinations using both the pretreatment molecular data and also the MF-adaptive response to radiation may provide an important role for focused radiation therapy as an integral part of precision medicine and immunotherapy.

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Where Do We Look for Markers of Radiotherapy Fraction Size Sensitivity?

Cited by 14 publications

References 103 publications

Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer

Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer

Hypofractionated whole breast radiotherapy: current perspectives

Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy

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