Local Control and Toxicity of External Beam Reirradiation With a Pulsed Low-dose-rate Technique

Lee, Charles T.; Lango, Miriam; Li, Tianyu; Freedman, S. Robert; Anaokar, Jordan; Galloway, Thomas J.; Hallman, M.A.; Weiss, Stéphanie; Hayes, S.B.; Price, Robert A.; Charlie, C.‐M.; Meyer, Joshua E.

doi:10.1016/j.ijrobp.2017.12.012

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…The use of PLDR irradiation in local recurrent HNSCC has been recently tested in a clinical trial in order to evaluate safety and treatment efficacy. [31][32][33] PLDR irradiation was initially proposed for the treatment of recurrent radioresistant gliomas. 13,16 It exploits two phenomena, LDHRS, and the inverse dose-rate effect.…”

Section: Discussionmentioning

confidence: 99%

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Todorović

Prevc

Žakelj

et al. 2020

Radiology and Oncology

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BackgroundManagement of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity.Materials and methodsCell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR.ResultsRadioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed.ConclusionsWe demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRS-positive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints.

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Section: Discussionmentioning

confidence: 99%

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Todorović

Prevc

Žakelj

et al. 2020

Radiology and Oncology

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“…In 2018, Lee et al reported on the use of PLDR in the reirradiation setting and found it to be effective and well tolerated. 22 As demonstrated in the figures, we use this technique frequently for cases in which we cannot meet OAR tolerance using the methods described, when an additional level of caution is needed, or when the gross tumor volume overlaps an OAR (eg, recurrent esophageal cancer).…”

Section: Discussionmentioning

confidence: 99%

Practical Clinical Implementation of the Special Physics Consultation Process in the Re-irradiation Environment

Price

Jin

Meyer

et al. 2021

Advances in Radiation Oncology

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Purpose The purpose of this work is to present a practical, structured process allowing for consistent, safe radiation therapy delivery in the re-treatment environment. Methods and materials A process for reirradiation is described with documentation in the form of a special physics consultation. Data acquisition associated with previous treatment is described from highest to lowest quality. Methods are presented for conversion to equieffective dose, as well as our departmental assumptions for tissue repair. The generation of organ-at-risk available physical dose for use in treatment planning is discussed. Results using our methods are compared with published values after conversion to biologically effective dose. Utilization of pulsed-low-dose-rate delivery is described, and data for reirradiation using these methods over the previous 5 years are presented. Results Between 2015 and 2019, the number of patients in our department requiring equieffective dose calculation has doubled. We have developed guidelines for estimation of sublethal damage repair as a function of time between treatment courses ranging from 0% for <6 months to 50% for >1 year. These guidelines were developed based on available spinal cord data because we found that 84% of organs at risk involved nerve-like tissues. The average percent repair used increased from 32% to 37% over this time period. When comparing the results obtained using our methods with published values, 99% of patients had a cumulative biologically effective dose below the limits established for acceptable myelopathy rates. Pulsed-low-dose-rate use over this period tripled with an average prescription dose of 49 Gy. Conclusions The methods described result in safe, effective treatment in the reirradiation setting. Further correlation with patient outcomes and side effects is warranted.

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“…Median progression-free survival (PFS) was 4.4 months (95% CI: 2.1-11.6) and OS was 14.3 months (95% CI: 6.7-undefined). A follow-up report included 39 patients treated between 2009 and 2016 (Lee et al 2018). The local progression rate was 16.5% at 6 months and 23.8% at 12 months.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Pulsed low dose-rate radiotherapy: radiobiology and dosimetry

Charlie¹

2022

Phys. Med. Biol.

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Pulsed low dose-rate radiotherapy (PLDR) relies on two radiobiological findings, the hyper-radiosensitivity of tumor cells at small doses and the reduced normal tissue toxicity at low dose rates. This is achieved by delivering the daily radiation dose of 2 Gy in 10 sub-fractions (pulses) with a 3-minute time interval, resulting in an effective low dose rate of 0.067 Gy/minute. In vitro cell studies and in vivo animal experiments demonstrated the therapeutic potential of PLDR treatments and provided useful preclinical data. Various treatment optimization strategies and delivery techniques have been developed for PLDR on existing linear accelerators. Preliminary results from early clinical studies have shown favorable outcomes for various treatment sites especially for recurrent cancers. This paper reviews the experimental findings of PLDR and dosimetric requirements for PLDR treatment planning and delivery, and summarizes major clinical studies on PLDR cancer treatments.

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Local Control and Toxicity of External Beam Reirradiation With a Pulsed Low-dose-rate Technique

Abstract: Reirradiation with PLDR is effective and well-tolerated. The risk of late toxicity and the durability of local control were limited by the relatively short follow-up duration in the present cohort.

Cited by 9 publications

References 38 publications

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity

Practical Clinical Implementation of the Special Physics Consultation Process in the Re-irradiation Environment

Pulsed low dose-rate radiotherapy: radiobiology and dosimetry

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