Salvage hypofractionated accelerated versus standard radiotherapy for the treatment of biochemical recurrence after radical prostatectomy (SHARE): the protocol of a prospective, randomized, open-label, superiority, multi-institutional trial

Background While several phase III trials have investigated the role of hypofractionated radiotherapy in the definitive treatment of localized prostate cancer, prospective data reporting the outcomes of hypofractionated radiotherapy in the postoperative treatment setting are sparse. Therefore, this study is designed to assess the efficacy and treatment-related toxicity of hypofractionated salvage radiotherapy for the treatment of biochemical recurrence in men who underwent radical prostatectomy. The primary objective of this trial is to investigate whether hypofractionated radiotherapy improves biochemical control compared with conventionally fractionated radiotherapy. In addition, treatment-related toxicity, quality of life, and survival will be evaluated as secondary endpoints. Methods In this prospective, randomized, multi-institutional trial (the SHARE study), patients with intermediate- or high-risk prostate cancer will be randomized to receive either hypofractionated radiotherapy (65 Gy in 2.5-Gy fractions) or conventionally fractionated radiotherapy (66 Gy in 2-Gy fractions). Prostate bed irradiation or elective pelvic nodal irradiation including the prostate bed will be performed using intensity-modulated radiotherapy and daily image guidance. Treatment efficacy will be assessed using the serum tumor marker prostate-specific antigen, and toxicity will be evaluated through both physician- and patient-reported outcomes. Quality of life will also be investigated. Discussion This study is designed to demonstrate whether hypofractionated radiotherapy is beneficial in terms of biochemical control and toxicity compared with standard salvage radiotherapy. If hypofractionated radiotherapy is shown to be superior to conventionally fractionated radiotherapy, it will mean that improved biochemical control can be achieved, accompanied by greater patient convenience and more efficient use of medical resources. Trial registration ClinicalTrials.gov NCT03920033. Registered on 18 April 2019

Evaluation of the Clinical Outcomes of Altered Fractionated Radiotherapy in Node Positive Breast Cancer (A Retrospective Study)

Background Hypofractionated radiotherapy schedules provide alternative shorter courses of radiotherapy of more than 2 Gy per fraction and lower total doses compared to the conventionally fractionated schedule of 1.8–2.0 Gy per fraction in 25 fractions. Hypofractionated radiotherapy offers the advantage of improving patients’ convenience and reducing cost and resource requirements. Aim To evaluate the efficacy and toxicity of hypofractionated radiotherapy compared to the conventional schedule. Methods In this retrospective study, the clinical data of 140 patients of node positive breast cancer patients were analyzed. Radiation toxicities and locoregional recurrence were compared between patients who received conventionally fractionated radiation schedule and those who received hypofractionated radiation schedules. Results After a median follow-up of 48 months, the incidence of loco-regional recurrence was comparable between the conventional and hypofractionated arms; 4% vs 3.1%, respectively (P-value = 0.769). Documented acute skin toxicity with ≥ grade 3 was found in 10.6% of the conventional group and in 5.6% of the hypofractionated group (p = 0.409). Grade 1 late lung toxicity was manifested in 6.1% of the conventional group and 7.5% of the hypofractionated group and G2 lung toxicity was found in one case only (1.9%) in the hypofractionated group (p = 0.596). Cardiac toxicity was documented in five cases; 9.4% and 5.1% in the conventional group and hypofractionated groups, respectively (pvalue=0.486). Conclusion Hypofractionated radiotherapy is comparable to conventional radiotherapy regarding locoregional tumor control and treatment toxicities.

Variability of α/β Ratios for Prostate Cancer With the Fractionation Schedule: Caution Against Using the Linear-Quadratic Model for Hypofractionated Radiotherapy

Background: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. Methods: The maximum likelihood principle in mathematical statistics was used to fit the parameters: k, α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification.Results: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI: 1.59-1.98, P < 0.001), 3.46 Gy (95% CI: 3.08-3.83, P < 0.001), and 4.24 Gy (95% CI: 4.10-4.39, P < 0.001), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased.Conclusions: The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.

Outcomes of pancreatic ductal adenocarcinoma (PDAC) patients treated with neoadjuvant stereotactic body radiation therapy (SBRT) or conventionally fractionated radiation therapy (CFRT).

e16209 Background: Hypothesis: Neoadjuvant SBRT can improve survival when compared to CFRT in PDAC patients who received chemotherapy. Past retrospective studies have shown improved outcomes of definitive SBRT when compared to CFRT without accounting for chemotherapy.1 We aim to study the outcomes of neoadjuvant SBRT vs CFRT accounting for chemotherapy. Methods: The National Cancer Database (NCDB) was queried for cases of PDAC from 2004-2015. Patients who received surgery and chemotherapy were included. Exclusion criteria were prior hormonal therapy or immunotherapy, lack of pathological confirmation or lack of information about chemotherapy. Log-rank test and Cox proportional hazards model were used to compare survival by radiation modalities. Predictors for overall survival (OS) were identified. Propensity score-matched (PSM) analysis balancing for different variables including type of chemotherapy was conducted. Results: Among 1604 patients, 223 (13.9%) had SBRT, and 1381 (86.1%) had CFRT. The median survivals were 30.0 and 26.0 months ( P = 0.010), while the 2-year survival rates were 63.4% and 53.7% for SBRT and CFRT patients, respectively. SBRT tended to be offered to older patients (age≥65: 56.1% vs 47.3%, P = 0.018), healthier patients (CCI=0: 72.2% vs 63.6%, P = 0.016), patients with worse cT staging (cT3 and cT4: 80.7% vs 69.7%, P = 0.008) and patients who got more multi-agent chemotherapy (89.2% vs 50.5%, P < 0.001). In the cohort with positive clinical lymph nodes (cN+), CFRT tended to decrease the pN staging more when compared to SBRT ( P = 0.032) (Table). In multivariate analysis, multi-agent chemotherapy (HR, 0.72; P < 0.001) was associated with better OS. SBRT did not show significantly better OS when compared to CFRT (HR, 0.81; P = 0.13) after accounting for other covariates including chemotherapy. PSM (1:1 match) analysis matched 223 pairs. SBRT did not show significant OS benefit (HR, 0.80; P = 0.17) when compared to CFRT. Conclusions: SBRT may be superior to CFRT in univariate analysis. However, after accounting for multi-agent chemotherapy, there is no significant survival difference between neoadjuvant SBRT and CFRT. Studies with larger sample size are desired. Neoadjuvant CFRT offers more significant nodal down-staging in patients with clinically positive lymph nodes (cN+) when compared to SBRT. Reference: Zhong J, Patel K, Switchenko J, et al. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotacticbody radiation therapy versus conventionally fractionated radiation. Cancer2017 Sep 15;123(18):3486-3493. pN staging of cN+ cohort[Table: see text]