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Purpose: Rectal spacers have gained popularity as a dose-sparing material for prostate cancer radiation therapy (RT). However, the procedure can be associated with unintended rectal wall infiltration (RWI) of the spacer gel. We therefore classified RWI severity as a function of depth and explored its association with rectal toxicity using a data set from prostate cancer patients treated with RT on a prospective randomized clinical trial (RCT)., Methods and Materials: Postimplant T2-weighted magnetic resonance images of 149 subjects randomized to the hydrogel spacer arm of a published multicenter RCT were assessed for the presence and depth of RWI. All implants were assigned a score of 0 (no rectal wall signal changes), 1 (rectal wall edema/signal change), 2 (partial RWI), or 3 (full-thickness RWI); RWI was defined as a score of 2 or 3. Correlations were made between RWI score and physician-reported procedure, acute, and late rectal toxicity., Results: Although 62.4% of implants had no rectal wall signal abnormalities, 24% [scores of 2 (20.1%) and 3 (4.0%)] of procedures exhibited radiographic evidence of RWI. Full-thickness RWI was associated with both a longer length (22.8 ± 7.0 mm, P = .008) and a larger circumferential percentage (35.8% ± 9.2%, P = .045) of rectal infiltration. Although 7 subjects (5%) experienced transient procedure-related rectal toxicities (most commonly perineal/rectal pain), only one had RWI (score of 2, National Cancer Institute's Common Terminology Criteria for Adverse Events grade 1). Consequently, no correlation was observed between procedural rectal toxicity and the presence/extent of RWI ( P = .64). Similarly, no difference in acute ( P = .64) or late ( P = .85) rectal toxicity incidence or grade was detected between RWI categories; none of the 6 men with a RWI score of 3 developed late rectal toxicity by 15 months., Conclusions: Based on data from an RCT, RWI did not contribute to increased rectal toxicity prior and up to 15 months after conventional prostate cancer RT., (© 2024 The Authors.)

Background: Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer., Objective: To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer., Design, Setting and Participants: Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day., Outcome Measurements and Statistical Analysis: The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure., Results and Limitations: The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity., Conclusions: SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment., Patient Summary: We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed., Methods: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk., Results: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%., Conclusion: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT)., Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated., Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P  = .002), maximum dose to 1 cc of rectum (D1cc; P  = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P  = .046) and ≥40 Gy (V40; P  = .005). SQS was also associated with a higher incidence of ( P  = .01) and highest-graded late rectal toxicity ( P  = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity., Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT., (© 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Background: Intermediate risk prostate cancer represents a largely heterogeneous group with diverse disease extent. We sought to establish rates of adverse pathological features important for radiation planning by analyzing surgical specimens from men with intermediate risk prostate cancer who underwent immediate radical prostatectomy, and to define clinical pathologic features that may predict adverse outcomes., Materials and Methods: A total of 1552 men diagnosed with intermediate risk prostate cancer who underwent immediate radical prostatectomy between 1/1/2005 and 12/31/2015 were reviewed. Inclusion criteria included available preoperative PSA level, pathology reports of transrectal ultrasound-guided prostate biopsy, and radical prostatectomy. Incidences of various pathological adverse features were evaluated. Patient characteristics and clinical disease features were analyzed for their predictive values., Results: Fifty percent of men with high risk features (defined as PSA >10 but <20 or biopsy primary Gleason pattern of 4) had pathological upstage to T3 or higher disease. The incidence of upgrade to Gleason score of 8 or higher and the incidence of lymph node positive disease was low. Biopsy primary Gleason pattern of 4, and PSA greater than 10 but less than 20, affected adverse pathology in addition to age and percent positive biopsy cores. Older age and increased percentage of positive cores were significant risk factors of adverse pathology., Conclusion: Our findings underscore the importance of comprehensive staging beyond PSA level, prostate biopsy, and CT/bone scan for men with intermediate risk prostate cancer proceeding with radiation in the era of highly conformal treatment., Competing Interests: The authors have declared that no competing interests exist.

Background: Effective patient provider communication skills can be difficult and time-consuming to teach. Deliberate practice of communication skills through improvisational theatre exercises, with structured debriefing, can provide a solution for teaching patient-centred communication skills in time-limited settings. The objective of this study was to determine if improvisational theatre exercises improved the ratings of patient satisfaction and empathetic communication by standardised patients., Methods: This was a randomised controlled trial looking at the effect of improvisational theatre exercises on ratings of patient satisfaction and empathetic communication. Third-year medical students (n = 188) participated in a formative team-based standardised patient (SP) experience. Prior to the SP experience, teams of students were randomly assigned to receive a 45-minute communication-focused improvisation intervention (immediately before the SP experience) or to a control arm without intervention. All teams then participated in the SP experience; the SPs (blinded to team randomisation assignment) then assessed each team's empathetic communication and completed patient satisfaction questions focused on physician behaviours derived from Press Ganey TM and the Hospital Consumer Assessment of Healthcare Providers and System Surveys TM . Fifty teams of three or four students participated; 20 teams in the intervention arm and 30 teams in the control arm., Results: Student teams in the improvisation intervention group had increased measures of empathetic communication (p = 0.04) compared to the control group. The intervention group had increased patient satisfaction survey ratings of 'ability to listen carefully' (p = 0.001) and of 'physician skills' compared to control groups (p = 0.03)., Discussion: Improv exercises with students increased students' empathetic communication and patient satisfaction as assessed by standardised patients., (© 2021 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Objectives: Although an association between meningioma and breast cancer (BC) has been postulated, clear mechanisms remain obscure. By conducting population-based analyses in women with both BC and meningioma, hypothesis-generating causal links were pursued., Methods: Using the US SEER 18 registry (2004 to 2009), clinicopathologic and demographic characteristics from cohorts of women with only BC (n=279,821) or meningioma (n=19,570) diagnoses were compared with 412 women with both diagnoses (BC-meningioma)., Results: BC diagnosis preceded meningioma by >2 months in 48% of women; 20% had synchronous (within 2 mo) disease. Median meningioma size was 1.9 and 2.4 cm in the BC-meningioma and meningioma cohorts, respectively (P=0.0009). Among BC-meningioma patients, meningioma size was similar whether diagnosed >2 months prior, synchronously, or >2 months after BC. Meningioma was pathologically confirmed in 38% of BC-meningioma and 51% of meningioma patients. Distribution of BC histologies was comparable in patients with and without meningioma, with ductal type predominating (80% in BC-meningioma, 83% in BC). Although hormone receptor status of invasive BC was not significantly different between BC-meningioma and BC groups, the BC-meningioma cohort had fewer women with ER+/PR+ in situ disease (P=0.006). BC stage among women with meningioma was more advanced versus women with BC only., Conclusions: Women with BC and meningioma have smaller-sized meningiomas and more advanced BCs compared with women having only 1 diagnosis. As there was no temporal relationship between size and latency between tumor diagnoses, the disparity in meningioma size between BC-meningioma and meningioma cohorts may have BC-associated biological components that warrant further study.

Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor(®))-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.