Dose-averaged linear energy transfer per se does not correlate with late rectal complications in carbon-ion radiotherapy

Abstract

Background and purpose: Several studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT. Materials and methods: Overall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible ''clinical dose"), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Nine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D 2cc in clinical dose was the sole risk factor for !grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D 2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting !grade 3 late rectal complications. Among 35 patients whose rectal D 2cc was !60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se. Conclusion: We demonstrated that severe rectal toxicities were related to the rectal D 2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se.

Carbon Ion Radiotherapy for Locally Recurrent Rectal Cancer of Patients with Prior Pelvic Irradiation

“…The dose constraints for the D2cc of the intestine and bladder were set at 50 Gy (RBE) and 60 Gy (RBE) in 16 fractions, respectively, and at 60 Gy (RBE) and 70 Gy (RBE) when combined with the dose distribution of the previous XRT, based on prior evaluations by Okonogi et al 15 and Kim et al 16 Examples of PTV with isodose distributions are shown in Fig. 1 .…”

Calculating dose‐averaged linear energy transfer in an analytical treatment planning system for carbon‐ion radiotherapy

“… 4 , 16 , 17 Furthermore, several recent studies have demonstrated the potential association of LETd of CIRT with tumour recurrence or normal tissue toxicities. 9 , 10 , 11 These suggest that clinical outcomes could be further improved by incorporating LETd in the planning optimization process. Although LETd can be derived through MC simulation, 18 measurements, 12 or analytic calculations, 19 evaluation or optimization of LETd in patients’ treatment plans remains challenging.…”

“…8 LETd also has been acknowledged as an indicator strongly correlated to the clinical outcome in cancer radiotherapy. 9 , 10 , 11 …”

“…8 LETd also has been acknowledged as an indicator strongly correlated to the clinical outcome in cancer radiotherapy. [9][10][11] However, LETd calculation has not been widely available. Although dedicated Monte-Carlo (MC) simulations have been used in some institutions, 12,13 accessing a fast MC engine for routine LETd calculation is naturally challenging for most of the particle therapy practitioners.…”

The Emerging Potential of Multi-Ion Radiotherapy

“…Okonogi and colleagues similarly considered uterine cancer, focusing on whether LET was correlative with late rectal toxicity rate ( 49 ). In evaluating 132 patients with CIRT-treated uterine carcinoma and greater than 6 months of follow-up, nine were noted to have grade 3 or 4 late rectal complications.…”