Introduction
Prostate cancer is expected to account for 21% of total new malignancies developing among men in USA during 2020(1). Several factors associated with increasing age, ethnicity, family history, genetic and hormonal influences, increase the probability of being diagnosed with carcinoma of the prostate gland (2). The presence of this malignancy can reduce the life expectancy and also compromise the quality of life of the patients due to sexual dysfunction, urinary incontinence and bowel problems. The improvements in early disease detection and treatment have reduced the mortality rate for prostate carcinoma by 52% since 1993 and have achieved a 5-year survival rate for all-stage disease of 98% (1). External-beam radiotherapy is extensively applied for the effective management of prostate cancer (2). At present, prostate irradiation is usually performed with the modern techniques of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). These modern approaches enable the delivery of high cumulative radiation doses to the tumor site using high-energy X-ray beams generated by a linear accelerator. Both IMRT and VMAT improve the quality of the patient's treatment plan and the sparing of the adjacent normal structures compared to conventional irradiation (3,4). A meta-analysis comparing the two aforementioned modulated techniques revealed that VMAT may be considered as the preferred approach to prostate cancer treatment due to its superior delivery efficiency (5).
VMAT is usually delivered with 6-MV photons in most radiation oncology centers (6). The use of 10-MV X-rays for arc therapy of prostate carcinoma has also been proposed (7-10). Pasler et al (7) demonstrated that the effect of beam energy on the target coverage and organ at risk (OAR) sparing is not significant. Different results were reported by other studies (8-10). Kleiner and Podgorsak (8) found that the use of 10-MV instead of 6-MV X-rays was associated with better conformity and sparing of the critical organs. Stanley et al (9) observed a faster dose fall-off with 10-MV photon beams. Mattes et al (10) also reported that the increase of photon beam energy resulted in dosimetric benefits. However, none of those studies discussed the issue of radiation-induced carcinogenesis due to the heavy irradiation of surrounding tissues.
The purpose of the present study was to examine the effect of 6-MV and 10-MV photon beam energies on the VMAT plan quality for prostate cancer, as well as on the relevant risk of secondary cancer induction.
Discussion
In the present study, the effect of 6-MV and 10-MV photons on the VMAT plans for prostate cancer and on the probability for developing secondary bladder or rectal malignancies were investigated. No attempts were made to use higher photon beam energies for treatment planning. It is well known that there is no neutron contamination when medical linear accelerators operate at 6-MV. The neutron production is also minimal for treatment with 10-MV X-rays (20). By contrast, the contribution of the neutron dose to the total dose of critical organs becomes significant when radiation therapy is delivered with 15-MV or 18 MV photon beams (20).
The DVH parameters of the two plans of each patient satisfied the previously published dose constraints (11,13). The differences in the mean values of the parameters related to PTV, OARs and surrounding normal tissues, as defined by the plans with 6-MV and 10-MV photon energies, were found to be rather small. The aforementioned minor discrepancies are consistent with the results of previous reports on IMRT (21) and VMAT (7) for prostate cancer. In the present study, the only noteworthy discrepancy between the plans generated with the two different photon energies was observed for the treatment delivery time. The mean value of the MUs calculated for 10-MV VMAT plans was by 11.8% lower compared with that associated with 6-MV treatment.
The lifetime risk for radiotherapy-induced bladder malignancies varied between 0.041 and 0.129% by the patient under investigation and the photon energy used for VMAT of prostate cancer. The corresponding probability for developing secondary rectal malignancies was 0.047-0.153%. The lifetime risks of carcinogenesis were estimated from a patient group with a mean age of 68 years subjected to hypofractionated VMAT for prostate carcinoma up to a dose of 70 Gy. Limited information has been published on the probability of developing secondary malignancies from prostate irradiation using hypofractionation schedules (13,22). The cancer risks of the present study are consistent with those of a previous report on hypofractionated treatment with 6-MV photons at the ages of 60 and 70 years (13), reporting lifetime bladder and rectal cancer risks of 0.06-0.18% and 0.07-0.20%, respectively. Stokkevag et al (22) provided a wide range of bladder and rectal cancer risks of 0.01-0.80% for 60-year-old patients receiving 67.5 Gy to the prostate and simultaneously 60 Gy to the seminal vesicles in 25 fractions with 6-MV VMAT. Their estimates were obtained with a linear-plateau association and a bell-shaped competition model. Bladder and rectal cancer risks from standard fractionated IMRT and VMAT for prostate carcinoma have also been reported (18,23,24). These theoretical risks were estimated for total tumor doses of 75.6-78.0 Gy in daily fractions of 1.8-2.0 Gy. Murray et al (18) and Fontenot et al (23) did not report lifetime risks of carcinogenesis. Sanchez-Nietto et al (24) reported lifetime probabilities of 0.4-0.5% from IMRT and VMAT for a prostate cancer patient aged 60 years.
The Bland-Altman statistical test revealed that the bladder cancer risk associated with arc therapy using the low photon energy may be up to 7.1% higher or 1.9% lower than the respective risk value from irradiation with the high energy of X-rays in 95% of the cases. The 95% limits of agreement for the rectal cancer risk were -0.5 and 1.9%. These narrow limits clearly indicate that the differences between the VMAT plans created with 6-MV and 10-MV photons in the assessment of the second cancer risks are minor.
The cancer risk assessments in the present study were carried out for the bladder and rectum, which are partly exposed to primary radiation during VMAT for prostate cancer. The use of data from treatment planning systems for out-of-field organ dose calculations is not recommended (25). Different approaches, based either on direct measurements using physical phantoms (26,27) or on Monte Carlo simulations (28), may be applied for assessing the out-of-field organ doses and the relevant probabilities of carcinogenesis. The relatively small sample of patients with low-risk prostate carcinoma should be considered as a limitation of the present study. It should be noted that this study provided lifetime bladder and rectal cancer risk estimates derived from the use of a non-linear mechanistic model introduced by Schneider et al (17). The model-based risk predictions may contain several uncertainties. These uncertainties are associated with the definition of the organ-specific parameters of the mechanistic model. The use of the absolute values of the model-based cancer risk predictions in clinical practice must be viewed with caution. The PTV of the study participants included only the prostate gland. Further studies are required to examine the effect of beam energy on the probability of carcinogenesis in prostate cancer patients irradiated at sites encompassing the seminal vesicles and/or pelvic lymph nodes (7,29).
In conclusion, the VMAT plans for low-risk prostate cancer patients generated with 6-MV or 10-MV photons were clinically equivalent in respect to target volume coverage and normal tissue sparing. The differences between the probabilities for developing secondary bladder and rectal malignancies due to pelvic VMAT with the low and high energy X-rays were found to be minimal. Therefore, the selection of the 10-MV photons may be considered as the optimal choice for prostate cancer treatment due to the reduction of the treatment time.