Search

PurposePresent knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning-based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate.Methods and materialsThe EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors.ResultsA total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes.ConclusionsOur results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendalls tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendalls tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Technological advances in MRI-guided radiation therapy (MRIgRT) have improved real-time visualization of the prostate and its surrounding structures over CT-guided radiation therapy. Seminal studies have demonstrated safe dose escalation achieved through ultrahypofractionation with MRIgRT due to planning target volume (PTV) margin reduction and treatment gating. On-table adaptation with MRI-based technologies can also incorporate real-time changes in target shape and volume and can reduce high doses of radiation to sensitive surrounding structures that may move into the treatment field. Ongoing clinical trials seek to refine ultrahypofractionated radiotherapy treatments for prostate cancer using MRIgRT. Though these studies have the potential to demonstrate improved biochemical control and reduced side effects, limitations concerning patient treatment times and operational workflows may preclude wide adoption of this technology outside of centers of excellence. In this review, we discuss the advantages and limitations of MRIgRT for prostate cancer, as well as clinical trials testing the efficacy and toxicity of ultrafractionation in patients with localized or post-prostatectomy recurrent prostate cancer.

PURPOSE OF REVIEW: Multimodality therapy including radical prostatectomy, radiation therapy, and hormone therapy are frequently deployed in the management of localized prostate cancer. We sought to perform a critical appraisal of the most contemporary literature focusing on the multimodality management of localized prostate cancer. RECENT FINDINGS: Men who are ideal candidates for multimodality therapy include those with unfavorable intermediate-risk disease, high-risk disease, and very high-risk disease. Enhancements in both systemic agents (including second-generation antiandrogens) as well as localized therapies (such as stereotactic body radiotherapy and brachytherapy) are refining the optimal balance between the use of systemic and local therapies for localized prostate cancer. Genomic predictors are emerging as critical tools for more precisely allocating treatment intensification with multimodality therapies as well as treatment de-intensification. Close collaboration among medical oncologists, surgeons, and radiation oncologists will be critical for coordinating evidence-based multimodality therapies when clearly indicated and for supporting shared decision-making in areas where the evidence is mixed.

Predictors of genitourinary toxicity after post-prostatectomy radiotherapy remain elusive. A previously defined germline DNA signature (PROSTOX) has shown predictive ability for late grade ≥ 2 GU toxicity after intact prostate stereotactic body radiotherapy. We explore whether PROSTOX would predict toxicity among patients receiving post-prostatectomy SBRT on a phase II clinical trial.

BackgroundRadiotherapy impacts the local immune response to cancers. Prostate Stereotactic Body Radiotherapy (SBRT) is a highly focused method to deliver radiotherapy often used to treat prostate cancer. This is the first direct comparison of immune cells within prostate cancers before and after SBRT in patients.MethodsProstate cancers before and 2 weeks after SBRT are interrogated by multiplex immune fluorescence targeting various T cells and macrophages markers and analyzed by cell and pixel density, as part of a clinical trial of SBRT neoadjuvant to radical prostatectomy.ResultsTwo weeks after SBRT, CD68, and CD163 macrophages are significantly increased while CD8 T cells are decreased. SBRT markedly alters the immune environment within prostate cancers.

313 Background: Advanced molecular PET/CT (mPET) studies are increasingly being utilized in conjunction with multiparametric MRI (mpMRI) to evaluate the burden of radiorecurrent disease in men who develop a biochemical recurrence following definitive radiotherapy (RT) for prostate cancer (PCa). However, radiographic concordance with pathologic confirmation of radiorecurrent disease in this setting is poorly described. We sought to conduct a patient-level analysis comparing concordance of radiographic and pathologic findings between mpMRI and mPET. Methods: Men who had previously undergone definitive RT for PCa and subsequently experienced treatment failure defined by the Phoenix definition were enrolled in a prospective registry study wherein radiographically identified local PCa recurrences were biopsied using mpMRI or mPET fusion (Artemis) with real-time ultrasound. Prior to biopsy, men underwent diagnostic imaging with mpMRI, advanced mPET (68Ga-PSMA-11 or 18F-FACBC), or both in order to identify a biopsy target. At least one imaging modality had to reveal a recurrent lesion based on PIRADS or PROMISE imaging classifications in order to prompt biopsy. Radiographic and pathologic findings were classified as either “treatment effect” or “recurrent disease”. Using biopsy as the reference standard, positive predictive value (PPV) was evaluated for mpMRI and mPET modalities separately. Results: Of 28 patients with radiographic recurrence on mpMRI or mPET, 10/28 (35.7%) exhibited treatment effect without evidence of active cancer on biopsy confirmation. Prostate adenocarcinoma was identified in 17/28 patient biopsies, whereas small cell prostate cancer was present in 1 patient. All 28 men underwent mpMRI prior to biopsy and 23/28 (82.1%) additionally underwent mPET; 19/23 (82.6%) underwent 68Ga-PSMA-11 and 4/23 (17.4%) were imaged with 18F-FACBC. Concordance in the assessment of recurrent disease between mpMRI and mPET was achieved in 12/23 (52.2%) men who underwent both imaging modalities. Among the 28 men who underwent mpMRI, PPV was 0.84, whereas PPV for the 23 men who underwent mPET was 0.70. Conclusions: In patients for whom clinical suspicion of radiorecurrence was high enough to warrant a biopsy, pre-biopsy mpMRI outperforms mPET in terms of PPV for detecting pathologically confirmed locally radiorecurrent PCa. Used in tandem, mpMRI and mPET might better select appropriate candidates for biopsy than either radiographic modality alone. While advanced mPET remains promising for detecting distant recurrences at the time of RT failure, biopsy confirmation following radiographic detection of local radiorecurrence remains essential for evaluating the true burden of local recurrence.

PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

PurposeBoth the superstructures of virtual discourse in radiation oncology and the entities occupying influential positions in the social media landscape of radiation oncology remain poorly characterized.Methods and materialsNodeXL Pro was used to prospectively sample all tweets with the hashtag #radonc every 8 to 10 days during the course of 1 year (December 4, 2018, to November 29, 2019). Twitter handles were grouped into conversational clusters using the Clauset-Newman-Moore community detection algorithm. For each sample period, the top 10 #radonc Twitter influencers, defined using betweenness centrality, were categorized. Influencers were scored in each sample period according to their top 10 influence rank and summarized with descriptive statistics. Linear regression assessed for characteristics that predicted higher influence scores among top influencers.ResultsIn the study, 684,000 tweets were sampled over 38 periods. #radonc tweets took on the crowd superstructure of a hub-and-spoke broadcast network formed when prominent individuals are widely repeated by many audience members. Professional societies were the most influential category of Twitter handles with an average influence score of 7.63 out of 10 (standard deviation [SD] = 1.94). When industry handles were present among top 10 influencers, they exhibited the second highest average influence scores (6.75, SD = 1.06), followed by individuals with scores of 5.28 (SD = 0.43). The categories of influencers were stable during the course of 1 year. The role of attending physician, radiation oncology specialty, male sex, academic practice, and US-based handles in North America were predictors of higher influence score.ConclusionsTwitter influencers in radiation oncology represent a diverse group of people and organizations, but male academic radiation oncologists based in North America occupy particularly influential positions in virtual communities broadly characterized as "hub and spoke" broadcast networks. Periodic network-based analyses of the social media discourse in radiation oncology are warranted to maintain an awareness of the handles that are influencing discussions on Twitter and ensure that social media utilization continues to contribute to the field of radiation oncology in a meaningful way.

PurposeTo determine the effect of daily shifts based on rigid registration to intraprostatic markers on coverage of boost doses delivered to gross nodal disease for prostate cancer.Methods and materialsSeventy-five cone beam computed tomographies (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the gross tumor volumes [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its intended prescription dose (dose covering 95% of a 3 mm planning target volume [PTV] expansion).ResultsForty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with conventional fractionation using volumetric-arc radiation therapy, and 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared with bony-based registration (P < .0001). Nodal displacement was significantly higher for fiducial-based registrations (P < .0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (P < .0001). On fiducial-based registrations, a 3 to 5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8 to 9 mm are required as a result of asymmetrical prostatic motion.ConclusionsLarge and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to intraprostatic markers. Alternative approaches such as adaptive replanning may be required to overcome these limitations.