Hypofractionated Radiotherapy For Prostate Cancer Research Articles

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: Nonrandomized comparison with conventional fractionation

Objectives To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. Materials and methods One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. Results All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT ( P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT ( P = 0.001) and higher PSA ( P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. Conclusions The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.

Effect of patient variation on standard- and hypo-fractionated radiotherapy of prostate cancer

Recent publications suggested that the α/β ratio in the well-known linear quadratic (LQ) model could be as low as 1.5 Gy for prostate cancer, indicating that prostate cancer control might be very sensitive to changes in the dose fractionation scheme. This also suggests that the standard-fractionation scheme based on large α/β ratios may not be optimal for the radio-therapeutic management of prostate cancer. Hypo-fractionated radiotherapy for prostate cancer has received more attention recently as an alternative treatment strategy, which may lead to reduced treatment time and cost. However, hypo-fractionated radiotherapy may be more sensitive to patient variation in terms of disease control than standard-fractionated radiotherapy. The variation of LQ parameters α and β for a patient population may compromise the outcome of the treatment. This effect can be studied by the introduction of the σα and σβ parameters, which are the standard deviations of Gaussian distributions around α0 and β0. The purpose of this study is to examine the effect of patient variation in α and β on tumour control probability for standard- and hypo-fractionated radiotherapy of prostate cancer. The tumour control probability based on the LQ model is calculated using parameters α, β, σα and σβ. Our results show that σα is an important parameter for radiotherapy fractionation, independent of the α/β ratio. A large σα will result in a significant increase in the radiation dose required to achieve the same 95% TCP. Compared with the standard-fractionated scheme, σα has a smaller effect on hypo-fractionated treatment at lower α/β ratios. On the other hand, for lower α/β ratios, the β term also plays a more important role in cell-killing and therefore the patient variation parameter σβ must be considered when designing a new dose fractionation scheme.

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: Correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding

To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.

Effect of patient variation on standard- and hypo-fractionated radiotherapy of prostate cancer

Recent publications suggested that the alpha/beta ratio in the well-known linear quadratic (LQ) model could be as low as 1.5 Gy for prostate cancer, indicating that prostate cancer control might be very sensitive to changes in the dose fractionation scheme. This also suggests that the standard-fractionation scheme based on large alpha/beta ratios may not be optimal for the radio-therapeutic management of prostate cancer. Hypo-fractionated radiotherapy for prostate cancer has received more attention recently as an alternative treatment strategy, which may lead to reduced treatment time and cost. However, hypo-fractionated radiotherapy may be more sensitive to patient variation in terms of disease control than standard-fractionated radiotherapy. The variation of LQ parameters alpha and beta for a patient population may compromise the outcome of the treatment. This effect can be studied by the introduction of the sigmaalpha and sigmabeta parameters, which are the standard deviations of Gaussian distributions around alpha0 and beta0. The purpose of this study is to examine the effect of patient variation in alpha and beta on tumour control probability for standard- and hypo-fractionated radiotherapy of prostate cancer. The tumour control probability based on the LQ model is calculated using parameters alpha, beta, sigmaalpha and sigmabeta. Our results show that sigmaalpha is an important parameter for radiotherapy fractionation, independent of the alpha/beta ratio. A large sigmaalpha will result in a significant increase in the radiation dose required to achieve the same 95% TCP. Compared with the standard-fractionated scheme, sigmaalpha has a smaller effect on hypo-fractionated treatment at lower alpha/beta ratios. On the other hand, for lower alpha/beta ratios, the beta term also plays a more important role in cell-killing and therefore the patient variation parameter sigmabeta must be considered when designing a new dose fractionation scheme.

Effect of patient variation on standard- and hypo-fractionated radiotherapy of prostate cancer

Recent publications suggested that the α/β ratio could be as low as 1.5 for prostate cancer, indicating that prostate cancer control might be more sensitive to changes in the dose fractionation scheme. This also suggests that the standard fractionation scheme based on large α/β ratios may not be optimal for the radiotherapeutic management of prostate cancer. Hypo-fractionated radiotherapy for prostate cancer has received more attention recently as an alternative treatment strategy, which may lead to reduced treatment time and cost.