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Background and purpose: This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (DP) and accumulated dose (DA) were utilized. Materials and methods: In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data. Results: IMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate-high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal DA-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder DP-NTCP projected a higher GU toxicity than DA-NTCP, with VMAT having the highest risk (p < 0.05). Conclusion: Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate-high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent. [ABSTRACT FROM AUTHOR]

Purpose: To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. Material and methods: A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. Results: The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Conclusions: Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities. [ABSTRACT FROM AUTHOR]

Background and purpose: Normal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetricmodulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used. Material and methods: DP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation. Results: For mild-severe (Grade =1) GI toxicity, the model generated similar parameters based on DA and DP DVH data (DA-D50:71.6 Gy vs DP-D50:73.4; DAm: 0.17 vs DP-m:0.19 and DA/P-n 0.04). The 95% CI for DA-D50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade =2) GI toxicity, DAD50 parameter was higher and had a narrower 95% CI (DA-D50:77.9 Gy, 95% CI:76.4-79.6 Gy vs DP-D50:74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade =1 late GU toxicity, D50 and n parameters for DA and DP were similar (DA-D50: 58.8 Gy vs DP-D50: 59.5 Gy; DA-n: 0.21 vs DP-n: 0.19) with a low AUC of<0.6. For Grade =2 late GU toxicity, similar NTCP parameters were attained from DA and DP DVH Data (DA-D50:81.7 Gy vs DPD50: 81.9 Gy; DA-n:0.12 vs DP-n:0.14) with an acceptable AUCs of >0.6. Conclusions: The achieved NTCP parameters using modern RT techniques and accounting for organmotion differs from QUANTEC reported parameters. DA-D50 of 77.9 Gy for GI and DA/DP-D50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade =2 toxicities especially for GI derived D50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore the role of four-dimensional (4D) transperineal ultrasound (TPUS) in the contouring of prostate gland with planning computed tomography (CT) images, in the absence of magnetic resonance imaging (MRI). Materials and methods: Five radiation oncologists (ROs) performed two rounds of prostate gland contouring (single-blinded) on CT-alone and CT/TPUS datasets obtained from 10 patients who underwent TPUS-guided external beam radiotherapy. Parameters include prostate volume, DICE similarity coefficient (DSC) and centroid position. Wilcoxon signed-rank test assessed the significance of inter-modality differences, and the intraclass correlation coefficient (ICC) reflected inter- and intra-observer reliability of parameters. Results: Inter-modality analysis revealed high agreement (based on DSC and centroid position) of prostate gland contours between CT-alone and CT/TPUS. Statistical significant difference was observed in the superior-inferior direction of the prostate centroid position (p = 0.011). All modalities yielded excellent inter-observer reliability of delineated prostate volume with ICC > 0.9, mean DSC > 0.8 and centroid position: CT-alone (ICC = 1.000) and CT/TPUS (ICC = 0.999) left-right (L/R); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 0.998) anterior-posterior (A/P); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 1.000) superior-inferior (S/I). Similarly, all modalities yielded excellent intra-observer reliability of delineated prostate volume, ICC > 0.9 and mean DSC > 0.8. Lastly, intra-observer reliability was excellent on both imaging modalities for the prostate centroid position, ICC > 0.9. Conclusion: TPUS does not add significantly to the amount of anatomical information provided by CT images. However, TPUS can supplement planning CT to achieve a higher positional accuracy in the S/I direction if access to CT/MRI fusion is limited. [ABSTRACT FROM AUTHOR]