Pulsed low dose-rate radiotherapy: radiobiology and dosimetry

Abstract

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.

Investigation of Dose-Rate Effects in Pulsed Low Dose Rate Radiotherapy

“…It was suggested that for malignancies that exhibit lowdose HSR, delivering therapy in a pulsed fashion by dividing the total dose into a number of pulses that are separated by a fixed time interval in which the dose per pulse is below the transition dose of about 0.5Gy could yield an increase in both TCP and normal tissue sparing. However, the effect of the time interval or the effective dose rate was not investigated and the current delivery schedule was chosen for clinical practicality [6]. The low-dose HRS effect may diminish as the total dose accumulates without sufficient time intervals between the pulses, resulting in the eventual accumulation of sufficient damage to induce repair and radiation resistance [12].…”

“…PLDR can also prove to be a viable treatment modality against tumors proximal to previously treated healthy tissues which might be near or at its tolerance of received radiation dose. A detailed review of the radiobiology and dosimetric requirements for the implementation of PLDR clinically has been presented by Ma [6].…”

“…Their analyses indicated that delivering therapy in a pulsed fashion by keep the dose per pulse below the transition dose and an effective dose rate of 0.067Gy/min could improve both TCP and normal tissue complication probability (NTCP). However, the effect of the time interval used for the pulsed dose rate scheme was not investigated, and the effective dose rate of 0.067Gy/min was adopted primarily for clinical practicability, e.g., to deliver a daily 2Gy dose in 30 min [6]. A number of in vitro studies were carried out to investigate cell survival for different tumors using similar pulsed dose delivery [8][9][10][11][12].…”

Dose‐rate dependence and IMRT QA suitability of EBT3 radiochromic films for pulse reduced dose‐rate radiotherapy (PRDR) dosimetry

“…Implementation of a PRDR program for VMAT can be challenged by machine deliverability. Ideally, the meter rate for a PRDR plan would be adjusted to ensure 6.67 cGy/min to the mean target dose per Ma et al 5 In Elekta systems like the Infinity series, equipped with the Integrity control system, meter rates are continuously variable enabling the meter rate to be programmed to achieve a dose rate adjusted beam. To address this issue, we have developed an alternative approach that enables subfraction-based VMAT delivery at higher meter rates.…”

Case report: Fractional brain tumor burden magnetic resonance mapping to assess response to pulsed low-dose-rate radiotherapy in newly-diagnosed glioblastoma

“…Pulsed low-dose-rate radiotherapy (pLDR) is a commonly used reirradiation technique for recurrent high-grade gliomas, but its upfront use with concurrent TMZ is currently under investigation ( 10 – 13 ). While other salvage therapies for recurrent high-grade glioma exist, including stereotactic radiosurgery, conformal external beam radiation, and brachytherapy, pLDR delivers radiation in subfractions at specific time intervals, taking advantage of the hyper-radiosensitivity of proliferating tumor cells to low doses of radiation, as well as the reduced toxicity to normal brain tissue ( 12 , 14 ). Currently, there is limited data on the radiographic response to pLDR.…”