Alexander Valdman

Background: The PRORECT trial compares proton and photon radiotherapy in rectal cancer. Purpose: To evaluate inter-observer agreement in gross tumor volume (GTV) delineation between a radiation oncologist and a radiologist in the PRORECT trial. In addition, we evaluated baseline tumor volume and length as predictors of clinical complete response (cCR) and compared tumor length and tumor and nodal staging (TN-stage) between diagnostic magnetic resonance imaging (dMRI) and treatment planning MRI (tpMRI). Material and Methods: A total of 50 consecutive patients underwent dMRI and tpMRI. GTV on tpMRI were delineated by a radiation oncologist (GTVo) and a radiologist (GTVr). Tumor lengths and TN staging were determined by the radiologist on both dMRI and tpMRI. Results: Patients underwent dMRI and tpMRI with a median interval of 23 days (range=10–51 days). Median GTVo and GTVr volumes were 41.3 cm ³ (range=3.7–149.9 cm ³ ) and 29.6 cm ³ (range=1.1–137 cm ³ ), respectively. The median Dice score was 0.75 (range=0.3–0.86). GTVo and GTVr were highly positively correlated (r(48) = 0.919; P < 0.001) and the median volume difference was significant (W, Z = −4.5214; P < 0.001). GTVr volume, but not tumor length, was significantly correlated with cCR ( r _pb = −0.395, n = 50; P = 0.005). Increasing GTVr was associated with reduced likelihood of achieving cCR. No changes in TN stage between dMRI and tpMRI were observed. Conclusion: The overall inter-observer agreement in GTV delineation between radiologist and radiation oncologist was good (median Dice score = 0.75 [range=0.3–0.86]). There was a small difference in measured tumor length between dMRI and tpMRI, but no change in TN stage between dMRI and tpMRI. GTVr was a significant predictor of achieving cCR.

Background: This study assesses the incidence and timing of undetectable prostate‐specific antigen (PSA) after radiotherapy (RT) ± androgen deprivation therapy (ADT) and its association with prostate cancer mortality.Methods: This is a population‐based study including 5299 men undergoing RT (2006–2020) in the Stockholm County, Sweden with all their PSA tests until death or emigration. The authors calculated incidence and timing of undetectable PSA (PSA ≤0.1 ng/mL) and used competing risk regression to evaluate the association of detectable PSA at 6 and 12 months with prostate cancer mortality (PCSM).Results: Median follow‐up for survivors was 81 (32, 130) months. PSA nadir values were reached before 6 and 12 months in 233 (23%) and 470 (36%) patients undergoing RT and 2871 (85%) and 3612 (90%) patients undergoing RT+ADT. No significant association was found between PSA at nadir, 6 and 12 months and PCSM in the radiotherapy group and evidence of association with higher PCSM in RT+ADT group (PSA at nadir: subdistribution hazard ratio [sHR], 2.23 [2.01–2.49]; PSA at 6 months: sHR, 6.91 [5.17–9.23]; and PSA at 12 months: sHR, 37.9 [23.0–62.5]). At 12 years after RT + ADT, PCSM rates were 27%, 15%, 13%, and 5% for patients with PSA at 6 months of ≥0.5, 0.2–0.5, 0.1–0.2, and ≤0.1 ng/mL, respectively; corresponding rates by PSA at 12 months were 34%, 18%, 12%, and 5%.Conclusions: Most patients undergoing RT+ADT reached a PSA ≤0.1 ng/mL within 6 and 12 months. PSA>0.1 ng/mL at these time points indicated a higher risk of PCSM, emphasizing the need for timely restaging and intensified salvage treatments.

Background/Objectives: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be possible. It is hypothesized that cCR rates will increase with increasing radiotherapy doses. By using proton therapy, doses to organs at risk (OAR) may be decreased. In preparation for a clinical trial on dose-escalated proton therapy for LARC, the purpose of this study is to establish the feasibility of proton therapy for dose-escalated hypofractionated radiotherapy of LARC. Methods: Ten patients, having previously received short course radiotherapy (SCRT) for LARC, were included in this planning study. Two photon plans and two proton plans were created for each patient: one with a standard 5 × 5 Gy fractionation and one dose-escalated up to 5 × 7 Gy. Proton plans were robustly optimized. For all plans the integral dose (ID) was computed, and for the proton plans relative biological effectiveness (RBE) distributions were calculated. Feasibility was assessed in terms of target coverage and OAR doses. Results: All treatment plans satisfied target coverage criteria. Three of the photon and two of the proton dose-escalated plans exceeded recommended OAR objectives. Proton IDs were on average lower by a factor of 1.97 compared to photon IDs. Mean doses to OAR were, in general, lower for protons. All proton RBE values in the escalated target volumes were between 1.09 and 1.16. Conclusions: The proposed dose escalation was found to be feasible. Protons can reduce the integral dose and mean doses to OARs compared to photons in both the dose-escalated and non-escalated cases. Differences in RBE between escalated and standard fractionation were small.

Introduction Non-operative management of early-stage rectal cancer is increasingly recognised as a subject of significant clinical and research interest. Contact X-ray brachytherapy (CXB) offers an alternative to surgery in appropriately selected cases. Current clinical evidence suggests the use of CXB in combination with chemoradiotherapy (CRT). Although proven effective, no randomised evidence exists for the combination of CXB and short-course radiotherapy (SCRT). In this Swedish national randomised phase II trial, we aim to compare the combination of CXB with either CRT or SCRT in patients with early-to-intermediate rectal cancer. Methods and analysis A total of 110 eligible, operable patients with early-to-intermediate rectal cancer (cT1–cT3ab), with tumours measuring Ethics and dissemination CORRECT is conducted in accordance with research ethical approval (2024-02762-01) granted by the Swedish Research Ethics Committee on 4 June 2024. Informed consent will be obtained from all trial participants. The trial results will be published in international peer-reviewed journals. Trial registration number NCT06501053.