Safety and tolerability of radiotherapy in combination with systemic targeted therapies for treatment of hepatocellular carcinoma: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC. METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC. KEY CONTENT AND FINDINGS: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy. CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.

Low-dose-rate brachytherapy and long-term treatment outcomes in patients younger than 60 years of age.

Purpose: Low-dose-rate (LDR) brachytherapy in young men remains controversial amongst urologists due to their concerns regarding long-term biochemical control and treatment-related toxicities. The purpose of this study was to evaluate the treatment outcomes of men under 60 years of age who underwent LDR brachytherapy with iodine-125 (125I) for clinically localized low- to intermediate-risk prostate cancer. Material and methods: All consecutive patients with clinically localized prostate cancer treated at our institution from 2003 to 2016 with 125I monotherapy were included in the study. Prescription dose was 145.0 Gy modified peripheral loading (MPD). All patients were assessed for biochemical progression-free survival using Phoenix definition (nadir +2 ng/ml), clinical progression-free survival, overall survival (OS), and any associated treatment toxicity. Results: A total of 161 patients were included, with a median follow-up of 6.8 years (range, 3-14.54 years). Median age at implant was 57 years (range, 53-59 years). Mean prostate specific antigen (PSA) level at diagnosis was 4.43 ng/ml (SD = 2.29). Majority of men had low-risk prostate cancer (70.2%). Biochemical progression-free survival at 8 years was 94% for the entire cohort. Median PSA at 4 years was 0.169 (IQR, 0.096-0.360), with 45% of patients having a PSA greater than 0.2. OS was 96.9%, with 5 deaths reported but only one was secondary to prostate cancer. Late grade > 2 genitourinary toxicities were reported in 18 patients (11.2%). Three patients (1.9%) developed secondary cancers, all considered unrelated to their LDR brachytherapy. Conclusions: With excellent long-term treatment outcomes and minimal associated toxicities, our results showed that LDR brachytherapy can be an effective treatment of choice in younger men.

Stabilised Hyaluronic Acid (sHA) gel as a novel marker for breast cancer tumour bed cavity: Surgical feasibility.

Introduction: Consistent delineation of the breast conserving surgery (BCS) tumour bed (TB) for breast cancer remains a challenge for radiation oncologists. Accurate delineation allows for better local control and reduces toxicity when planning partial breast or TB boost radiation therapy (RT). Methods: In the operating theatre (OT) breast surgeons inserted stabilised hyaluronic acid (sHA) gel as small drops approximately one cm into the walls surrounding the resection cavity. Surgical feasibility was determined by the rate of successful sHA gel insertion procedure, the ease of insertion as rated by surgeons, the time required for insertion procedure, the quantity used, and any adverse events (AE) relating to sHA gel insertion. Results: Thirty-five patients were enrolled. All patients underwent sHA gel insertion successfully. The procedure added a median of 2.8 min to the OT time and was rated as 'easy' in 89 % of patients. There were no immediate AE in OT. Five (14 %) patients experienced a grade 2 or higher AE. Three of the five patients were prescribed oral antibiotics for breast infection. Two of the five patients experienced a grade 3 AE - haematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS. All five patients recovered and underwent the planned adjuvant therapies for their BC. The AE data reflects common risks with standard BCS and are not clearly attributed to sHA gel insertion alone. Conclusion: We show that sHA gel is surgically feasible as a marker to help define the TB cavity for post-BCS adjuvant MRI-based RT planning.

Application of a Radiopaque Viscous Hydrogel Spacer for Prostate Cancer Radiation Therapy: A Prospective Phase 2 Study.

PURPOSE: The aim of this study was to evaluate the application of a radiopaque viscous spacer (RVS) for prostate cancer radiation therapy (RT), including injection procedure, toxicity, treatment planning, image guidance, and imaging results up to 12 months after RT. METHODS AND MATERIALS: RVS (median, 10 mL) was injected between prostate and rectal wall in 30 patients. Cone beam computed tomography (CT) was performed during the course of RT, a magnetic resonance imaging 3 and 12 months after RT. Injection and treatment tolerability were analyzed. The resulting distribution was compared with a control group of 30 patients with an initially fluid spacer. RESULTS: Procedure- or device-related adverse events were not observed. Signs of hydrogel migration were not found in any case. The volume decreased by 25% at 3 months after RT, and small residues were detected at 12 months after RT in 3 cases (10%). The median rectal volume percentage within the 90% isodose was 3.0% (interquartile range, 1.5%-4.5%). Acute and late gastrointestinal toxicities were found in 17% and 3%, respectively (all grade 1). The median distance between prostate and rectum at the base/midplane/apex was greater for RVS in comparison to initially fluid spacer (14/12/11 mm vs 12/10/10 mm, respectively), the gel symmetry (right vs left from midline) was comparable. The application was assessed to be easier to control by the users, and visibility in cone beam CT as good. CONCLUSIONS: The injection of a radiopaque viscous hydrogel spacer resulted in a prostate-rectum distance of >10 mm in most cases. The resulting rectum volume within the high-dose region and RT toxicity were very low. Advantages in comparison to the conventional hydrogel spacer are predominantly an improved placement control during the injection process and good visibility on CT.

CD8+ lymphocytes are critical for early control of tuberculosis in macaques.

The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired early control of Mycobacterium tuberculosis (Mtb) infection, leading to increased granulomas, lung inflammation, and bacterial burden. Analysis of barcoded Mtb from infected macaques demonstrated that depletion of all CD8+ lymphocytes allowed increased establishment of Mtb in lungs and dissemination within lungs and to lymph nodes, while depletion of only adaptive CD8+ T cells (with anti-CD8ß antibody) worsened bacterial control in lymph nodes. Flow cytometry and single-cell RNA sequencing revealed polyfunctional cytotoxic CD8+ lymphocytes in control granulomas, while CD8-depleted animals were unexpectedly enriched in CD4 and γδ T cells adopting incomplete cytotoxic signatures. Ligand-receptor analyses identified IL-15 signaling in granulomas as a driver of cytotoxic T cells. These data support that CD8+ lymphocytes are required for early protection against Mtb and suggest polyfunctional cytotoxic responses as a vaccine target.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the overall efficacy of StrataXRT, a topical gel dressing, in preventing acute radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy (RT). METHODS: A systematic search was conducted on April 25, 2023 in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing the effectiveness of StrataXRT in preventing acute RD in breast cancer patients undergoing adjuvant RT to the breast or chest wall with or without regional nodes were included. Pooled incidence odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model, with analysis and forest plots generated in RevMan v5.4. RESULTS: The analysis included three RCTs with a total of 189 patients assessed using per-protocol analysis. Two RCTs compared StrataXRT to standard of care, while the third compared it with Mepitel film and was reported separately. In the former RCTs, the odds ratio (OR) for developing acute grade 3 RD favored StrataXRT at 0.05 (95% CI, 0.01-0.22; P < 0.0001). The OR for developing acute grades 2-3 RD was 0.32 (95% CI, 0.03-3.18; P = 0.33). The RCT comparing StrataXRT with Mepitel film showed insignificant ORs for grade 3 and grades 2-3 RD. One RCT reported significantly lower erythema index (P = 0.008) and melanin index (P = 0.015) in StrataXRT patients. The use of StrataXRT did not raise additional safety concerns. CONCLUSION: StrataXRT may help prevent severe acute RD in breast cancer RT patients. Further high quality, large-scale studies are needed to confirm these findings.

Effects of aromatase inhibitor therapy on adiposity and cardiometabolic health in postmenopausal women: a controlled cohort extension study.

Purpose: We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body composition or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods: We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results: Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was -1.54 cm2 (95% CI: -14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increases in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and exploratory outcomes was observed between groups. Conclusions: While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-associated effect and more on the general development of cardiovascular risk over time.

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial.

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT. Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT. Design, Setting, and Participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to µg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality. Main Outcomes and Measures: For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%. Results: Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01). Conclusions and Relevance: The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT. Trial Registration: ClinicalTrials.gov Identifier: NCT04189913.

Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective.

PURPOSE: To assess the degree of pathologic complete response (pCR), postoperative surgical complication rates, and oncological outcomes in women with locally advanced breast cancer or high-risk breast cancers treated with neoadjuvant radiation therapy (NART). METHODS AND MATERIALS: This retrospective, multi-institutional review involved 138 clinically staged patients with 140 breast cancers treated with NART between January 2014 and February 2021. Treatments involved sequential neoadjuvant chemotherapy and NART, followed by mastectomy with or without axillary surgery and immediate autologous breast reconstruction. Descriptive statistics were used to assess patient and disease features, treatment regimens, pathologic response, and factors affecting postoperative complications. Kaplan-Meier curves were performed to assess locoregional recurrence-free, distant metastasis-free, and overall survival outcomes. RESULTS: Median age was 47 years (interquartile range, 42-52). The median follow-up was 35.2 months (interquartile range, 17.1-46.5). pCR was achieved in 36.4% (as defined by Chevallier classification) or 42.1% (as defined by Miller-Payne scores) of patients. Greater pCR rates were achieved for HER2+ (73.8%-85.7%) and triple-negative phenotypes (47.6%-57.1%). There were 21 grade 3 surgical complications including 10 grade 3B breast events and 8 grade 3B donor-site events, where surgical reintervention was required. At 3-years' follow-up, the locoregional recurrence-free survival was 98.1%, distant metastasis-free survival was 83.6%, and overall survival was 95.3%%. CONCLUSIONS: NART is feasible to facilitate a single-stage mastectomy and immediate autologous breast reconstruction. This study demonstrated comparable rates of postoperative complication to standard of care, and high rates of pCR, which translates to high rates of locoregional control, distant metastasis-free survival, and overall survival.

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer.

OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

PSMA-PET Detection of Unusual Metastases in Castrate-Sensitive Prostate Carcinoma.

ABSTRACT: Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.

Effects of aromatase inhibitor therapy on visceral adipose tissue area and cardiometabolic health in postmenopausal women with early and locally advanced breast cancer.

OBJECTIVE: Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT. METHODS: We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed. RESULTS: In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cm2 (-16.9, 6.91), p = .55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12 months. Findings were similar after adjustments for activity levels and coronavirus disease 2019 lockdown duration. CONCLUSIONS: These data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.

CD4+ T cells are homeostatic regulators during Mtb reinfection.

Immunological priming - either in the context of prior infection or vaccination - elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior Mtb infection elicits a long-lasting protective response against subsequent Mtb exposure and that the depletion of CD4+ T cells prior to Mtb rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4+ T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4+ T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8+ T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating Mtb disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4+ and CD8+ T cells, but also modulate innate immune cells to limit Mtb disease.

Hyaluronic acid rectal spacer in EBRT: Usability, safety and symmetry related to user experience.

OBJECTIVES: To report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy. PATIENTS AND METHODS: 102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed. RESULTS: HA insertion was completed with a 100% success rate independent of user experience, rated as 'easy' or 'very easy' in all cases. There were no postoperative complications reported. The mean (SD) recto-prostatic separation for all patients at the base, midgland and apex were 12 (±2) mm, 11 (±2) mm, and 9 (±1) mm respectively. The mean sagittal length of the implant was 43 (±5) mm. The implant was rated as symmetrical in 98% of cases. The mean rV70Gy was 1.6% (IQR 0.8-3.3%) for patients receiving 78-80Gy. The mean rV53Gy was 2.8% (IQR 1.2-4.8%) for patients receiving 60-62Gy. The median prostate size was 43.5 cc (IQR 32-57). CONCLUSION: Injection of HA was able to achieve highly symmetrical recto-prostatic separation, with new users able to produce excellent separation, particularly at the apex, achieving similar dosimetry outcomes as competent and experienced users. HA is safe, easy to use, and significantly reduced mean rV70Gy and rV53Gy compared to non-spacer patients.

Case Report: Reversal of Hyaluronic Acid Rectal Wall Infiltration with Hyaluronidase.

Peri-rectal spacers provide protection to the rectum for patients receiving radiation therapy treating prostate cancers. Commonly used hydrogel spacers hold the disadvantage that they cannot be readily reversed should inadvertent injection outside of the target area occurs, potentially leading to ischemia of the rectal mucosa leading to severe pain and ulceration, which can then lead to superinfection and pelvic abscess formation, and subsequently recto-prostatic fistulas. This could require major surgical intervention. New hyaluronic acid spacers are readily reversible with hyaluronidase and provide a valuable means to correct any misinjected spacer. We present a patient with prostate cancer who was planned for radiation therapy and required a rectal spacer. The hyaluronic acid rectal spacer was injected in part into the rectal wall. The patient was asymptomatic, and a sigmoidoscopy confirms healthy bowel mucosa only. The misinjected hyaluronic acid was successfully treated with targeted injection of hyaluronidase into only the rectal wall portion. Serial follow-up imaging demonstrated rapid dissolution of the misinjected hyaluronic acid with the well-positioned hyaluronic acid remaining. The patient did not experience any side effects of the hyaluronidase.

Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.

Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.

Changes in Management After 18F-DCFPyL PSMA PET in Patients Undergoing Postprostatectomy Radiotherapy, with Early Biochemical Response Outcomes.

Prostate-specific membrane antigen (PSMA) tracers have increased sensitivity in the detection of prostate cancer, compared with conventional imaging. We assessed the management impact of 18F-DCFPyL PSMA PET/CT in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and report early biochemical response in patients who underwent radiation treatment. Methods: One hundred patients were enrolled into a prospective study, with a prior RP for prostate cancer, a PSA of 0.2-2.0 ng/mL, and no prior treatment. All patients underwent diagnostic CT and PSMA PET/CT, and management intent was completed at 3 time points (original, post-CT, and post-PSMA) and compared. Patients who underwent radiotherapy with 6-mo PSA response data are presented. Results: Ninety-eight patients are reported, with a median PSA of 0.32 ng/mL (95% CI, 0.28-0.36), pT3a/b disease in 71.4%, and an International Society of Urological Pathology grade group of at least 3 in 59.2%. PSMA PET/CT detected disease in 46.9% of patients, compared with 15.5% using diagnostic CT (PSMA PET, 29.2% local recurrence and 29.6% pelvic nodal disease). A major change in management intent was higher after PSMA than after CT (12.5% vs. 3.2%, P = 0.010), as was a moderate change in intent (31.3% vs. 13.7%, P = 0.001). The most common change was an increase in the recommendation for elective pelvic radiation (from 15.6% to 33.3%), nodal boost (from 0% to 22.9%), and use of concurrent androgen deprivation therapy (ADT) (from 22.9% to 41.7%) from original to post-PSMA intent because of detection of nodal disease. Eighty-six patients underwent 18F-DCFPyL-guided radiotherapy. Fifty-five of 86 patients either did not receive ADT or recovered after ADT, with an 18-mo PSA response from 0.32 to 0.02 ng/mL; 94.5% of patients had a PSA of no more than 0.20 ng/mL, and 74.5% had a PSA of no more than 0.03 ng/mL. Conclusion: 18F-DCFPyL PET/CT has a significant impact on management intent in patients being considered for salvage radiotherapy after RP with PSA recurrence. Increased detection of disease, particularly in the pelvic lymph nodes, resulted in increased pelvic irradiation and concurrent ADT use. Early results in patients who are staged with 18F-DCFPyL PET/CT show a favorable PSA response.

A clinical study comparing polymer and gold fiducials for prostate cancer radiotherapy.

Introduction: Image guidance with gold fiducials improves outcomes of prostate radiotherapy. However, gold produces artefact on CT imaging, interfering with contouring and verification. The purpose of this study was to compare polymer to standard gold fiducials using radiotherapy imaging modalities to assess the visibility and artefact. Methods: Twenty eight patients with locally advanced prostate cancer were enrolled, half had three polymer fiducials implanted into the prostate and half underwent insertion of gold fiducials. Patients were imaged with CT, T2 weighted MRI, cone-beam CT (CBCT) and planar KV images. Fiducials were scored for visibility and assessed for CT artefact in surrounding prostate tissue. The artefact was quantified from Hounsfield number histograms and separated into percentile ranges and proportion of voxels in HU normal tissue range of a 2cm sphere surrounding the fiducial. Results: Gold and polymer fiducials were sufficiently visible for CT and CBCT verification. The gold fiducials could be visualized well on KV planar imaging; however, the polymer markers were obscured by pelvic bones. Neither polymer nor gold fiducials could be visualized on MRI. The polymer fiducial produced less artefact than gold on CT, having less voxel spread for the HU percentile ranges and a greater proportion of voxels in the normal tissue range. Conclusions: Polymer fiducials are a more suitable fiducial than gold for CT/CBCT in prostate cancer radiotherapy, demonstrating minimal artefact and good visibility on CT. However, they were not well seen on MRI or KV imaging and thus not suitable for co-registration or planar KV verification.