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Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT., Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%., Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation., Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We have developed a novel imaging analysis procedure that is highly predictive of local failure after chemoradiation in head and neck cancer. In this study we investigated whether any pretreatment biomarkers correlated with key imaging parameters., Methods: Pretreatment biopsy material was available for 28 patients entered into an institutional trial of adaptive radiotherapy in which FDG-PET images were collected weekly during treatment. The biopsies were immunohistochemically stained for CD44, EGFR, GLUT1, ALDH1, Ki-67 and p53 and quantified using image analysis. Expression levels were correlated with previously derived imaging parameters, the pretreatment SUV max and the dose response matrix (DRM)., Results: The different parameters of the SUV max and DRM did not correlate with each other. We observed a positive and highly significant (p = 0.0088) correlation between CD44 expression and volume of tumor with a DRM greater than 0.8. We found no correlation between any DRM parameter and GLUT1, p53, Ki-67 and EGFR or ALDH1. GLUT1 expression did correlate with the maximum SUV 0 and the volume of tumor with an SUV 0 greater than 20., Conclusions: The pretreatment SUV max and DRM are independent imaging parameters that combine to predict local recurrence. The significant correlation between CD44 expression, a known cancer stem cell (CSC) marker, and volume of tumor with a DRM greater than 0.8 is consistent with concept that specific foci of cells are responsible for tumor recurrence and that CSCs may be randomly distributed in tumors in specific niches. Dose painting these small areas may lead to improved tumor control., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest associated with this manuscript, (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To quantify inter/intra-tumoral variations of baseline metabolic activity and dose response. To evaluate their impact on tumor control and treatment dose prescription strategies., Methods and Materials: Tumor voxel baseline metabolic activity, SUV 0 , and dose response matrix, DRM, quantified using the pre-treatment and weekly FDG-PET/CT imaging feedback for each of 34 HNSCC patients (25 HPV+ and 9 HVP-) were evaluated. Inter/intra-tumoral variations of tumor voxel (SUV 0 , DRM) for each of the HPV- and HPV+ tumor groups were quantified and used to evaluate the variations of individual tumor control probabilities and the efficiency of uniform vs non-uniform treatment dose prescription strategies., Results: Tumor voxel dose response variation of all tumor voxels assessed using FDG-PET/CT imaging feedback had the mean(CV) = 0.47(47%), which was consistent with those of previously published in vitro tumor clonogenic assay. The HPV- tumors had the mean(CV) dose response, 0.53(49%), significantly larger than those of the HPV+ tumors, 0.45(43%). However, their baseline SUVs were opposite, 6.5(56%) vs 7.7(65%). Comparing to the inter-tumoral variations, both HPV-/+ tumor groups showed larger intra-tumoral variations, (53%, 58%) vs (20%, 31%) for the baseline SUV and (38%, 37%) vs (31%, 21%) for the dose response. Due to the large dose response variations, treatment dose to control the tumor voxels has very broad range with CV of TCD 50  = 97% for the HPV- and 67% for the HPV+ tumor group respectively. As a consequence, heterogeneous prescription dose could potentially reduce the treatment integral dose for 92% of the HPV+ tumors and 78% of the HPV- tumors., Conclusions: The study demonstrates that tumor dose response assessed using FDG-PET/CT feedback images had a similar distribution to those assessed conventionally using in vitro tumor clonogenic assay. Inter-tumoral dose response variation seems larger for HPV- tumors, but intra-tumoral dose response variations are similar for both HPV groups. These variations cause very large variation on the individual tumor control probability and limit the efficacy of dose escalation and de-escalation in conventional clinical practice. On the other hand, heterogeneous dose prescription guided by metabolic imaging feedback has a potential advantage in radiotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer., Methods: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process., Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR., Conclusions: In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)