Second malignant neoplasm risk after craniospinal irradiation in X-ray-based techniques compared to proton therapy.

Cranio-spinal irradiation (CSI) is widely used for treating medulloblastoma cases in children. Radiation-induced second malignancy is of grave concern; especially in children due to their long-life expectancy and higher radiosensitivity of tissues at young age. Several techniques can be employed for CSI including 3DCRT, IMRT, VMAT and tomotherapy. However, these techniques are associated with higher risk of second malignancy due to the physical characteristics of photon irradiation which deliver moderately higher doses to normal tissues. On the other hand, proton beam therapy delivers substantially lesser dose to normal tissues due to the sharp dose fall off beyond Bragg peak compared to photon therapy. The aim of this work is to quantify the relative decrease in the risk with proton therapy compared to other photon treatments for CSI. Ten anonymized patient DICOM datasets treated previously were selected for this study. 3DCRT, IMRT, VMAT, tomotherapy and proton therapy with pencil beam scanning (PBS) plans were generated. The prescription dose was 36 Gy in 20 fractions. PBS was chosen due to substantially lesser neutron dose compared to passive scattering. The age of the patients ranged from 3 to 12 with a median age of eight with six male and four female patients. Commonly used linear and a mechanistic doseresponse models (DRM) were used for the analyses. Dose-volume histograms (DVH) were calculated for critical structures to calculate organ equivalent doses (OED) to obtain excess absolute risk (EAR), life-time attributable risk (LAR) and other risk relevant parameters. A α' value of 0.018 Gy-1 and a repopulation factor R of 0.93 was used in the mechanistic model for carcinoma induction. Gender specific correction factor of 0.17 and - 0.17 for females and males were used for the EAR calculation. The relative integral dose of all critical structures averaged were 6.3, 4.8, 4.5 and 4.7 times higher in 3DCRT, IMRT, VMAT and tomotherapy respectively compared to proton therapy. The mean relative LAR calculated from the mean EAR of all organs with linear DRM were 4.0, 2.9, 2.9, 2.7 higher for male and 4.0, 2.9, 2.8 and 2.7 times higher for female patients compared to proton therapy. The same values with the mechanistic model were 2.2, 3.6, 3.2, 3.8 and 2.2, 3.5, 3.2, 3.8 times higher compared to proton therapy for male and female patients respectively. All critical structures except lungs and kidneys considered in this study had a substantially lower OED in proton plans. Risk of radiation-induced second malignancy in Proton PBS compared to conventional photon treatments were up to three and four times lesser for male and female patients respectively with the linear DRM. Using the mechanistic DRM these were up to two and three times lesser in proton plans for male and female patients respectively.

Radiation-Induced Second Cancer Risk from External Beam Photon Radiotherapy for Head and Neck Cancer: Impact on in-Field and Out-of-Field Organs

The purpose of this paper is to provide data on development of second primary cancers within or adjacent to tissue irradiated in the treatment of primary head and neck cancers using different techniques and modalities. Materials and methods: We selected five patients with HandN tumors located in base of the tongue for risk assessment. In order to examine the impact of choices of various planning techniques, numbers of beams and beam energy used in treatment plans - 7 and 9 field Intensity modulated radiotherapy (IMRT) plans using 6MV and 10 MV beam energies and a 6MV Volumetric modulated arc therapy (VMAT) plans were planned. Out-of-field measurements for secondary photon doses for the treatment plans were measured using diode-dosimeters and solid water slabs. Differential dose-volume histograms (DVH) for all 5 patients and 5 techniques, were exported and used to calculate organ equivalent dose (OAR), excess absolute risk (EAR), and life-time attributable risk (LAR) for in-field organs. Results: For all treatment plans, the DVH showed clinically acceptable values; adequate clinical target coverage and dose constraints were met for all organs at risk. There was a clear advantage for the VMAT plan; it provided superior organ at risk (OAR) sparing and adequate target coverage. VMAT has relatively low monitor units at 0.93±0.034 times 7F6. The average percentage scattered to prescription doses for the five patients at 15, 30, 45, 60 and 75 cm from the isocenter were 0.9212 ± 0.115, 0.2621 ± 0.080, 0.1617 ± 0.057, 0.0936 ± 0.026, 0.0296 ± 0.014, for VMAT. Conclusion: Organ-specific LAR was higher with VMAT compared to 7F6 for skin. 6-MV VMAT is an acceptable alternative to IMRT for HandN cancer and offers advantages in terms of sparing adjacent OAR.

Estimating Second Malignancy Risk in Intensity-Modulated Radiotherapy and Volumetric-Modulated Arc Therapy using a Mechanistic Radiobiological Model in Radiotherapy for Carcinoma of Left Breast.

OBJECTIVES: The aim of this study is to estimate second cancer risk (SCR) in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using a mechanistic radiobiological model. The model also takes into account patient age at exposure and the gender-specific correction factors of SCR. MATERIALS AND METHODS: Fifty IMRT and VMAT plans were selected for the study. Monte Carlo-based dose calculation engine was used for dose calculation. Appropriate model parameters were taken from the literature for the mechanistic model to calculate excess absolute risk (EAR), lifetime attributable risk, integral dose and relative risk (RR) for lungs, contralateral breast, heart, and spinal cord. RESULTS: The mean monitor unit (MU) in IMRT and VMAT plans were 751.1 ± 133.3 and 1004.8 ± 180, respectively, for IMRT and VMAT. The mean EAR values with age correction were 44.6 ± 11.9, 11.2 ± 6.4, 5.4 ± 4.0, 1.4 ± 0.5, and 0.3 ± 0.2 for left lung, right lung, contralateral breast, heart, and spinal cord, respectively, for the IMRT treatments and 54.6 ± 20.6, 30.2 ± 12.0, 13.8 ± 8.6, 1.6 ± 0.6, and 0.9 ± 0.5 for the VMAT treatments in units of 10,000 PY. The RR of 6.7% and 9.1%, respectively, for IMRT and VMAT found in our study using computational models is in close comparison with the value reported in a large epidemiological breast cancer study. CONCLUSIONS: VMAT plans had a higher risk of developing second malignancy in lung, contralateral breast, heart, and cord compared to IMRT plans. However, the increase in risk was found to be marginal compared to IMRT. Incorporating the age correction factor decreased the risk of contralateral breast SCR. No strong correlation was found between EAR and MU.