Sunnybrook Health Science Centre

In the PACE-B study, a nonrandomized comparison of toxicity outcomes between stereotactic body radiation therapy (SBRT) platforms revealed fewer urinary side effects with CyberKnife (CK) compared with conventional linac (CL) SBRT. This analysis compares baseline characteristics and planning dosimetry between the CK-SBRT and CL-SBRT cohorts in PACE-B, aiming to provide insight into possible reasons for differing toxicity outcomes between the platforms. Dosimetric parameters for the surrogate urethra (SU), contoured urethra, bladder, bladder trigone (BT), and rectum were extracted from available computed tomography planning scans of PACE-B SBRT patients. The SU and BT were retrospectively delineated. Dose levels analyzed included maximum point dose (Dmax), D2, D50, and D95, where D(n) represents the dose (Gy) to (n)% of the structure. Baseline characteristics and planning dosimetry between the CK-SBRT and CL-SBRT cohorts were compared using Mann-Whitney U tests, t tests, and χ2 tests. Of the 414 patients who received SBRT, 169 (41%) were treated with CK-SBRT and 245 (59%) with CL-SBRT, with dosimetric parameters available for 94% of patients (390/414). There was a nonstatistically significant trend toward more low-risk prostate cancer in the CK-SBRT cohort (12% vs 6% P = .02 [nonsignificant]). Margins were similar between platforms, except posteriorly, where CK-SBRT had smaller margins. CK-SBRT plans had significantly higher median SU Dmax (45.9 Gy vs 42.8 Gy, P < .0001), D2%, and D50% compared with CL-SBRT plans. Additionally, CK-SBRT plans had significantly higher median BT Dmax (43.4 Gy vs 41.6 Gy, P < .0001), D2%, and D95%, as well as higher median bladder Dmax, D50%, and D95%. CK-SBRT plans had lower median rectal D2% (35.5 Gy vs 36.0 Gy, P < .0001) but higher rectal D50% and D95%. Although the CK-SBRT cohort showed lower urinary toxicity, the planned doses to urinary substructures were actually higher, likely due to heterogeneous dose planning. Factors like intrafraction tracking or other confounding variables may explain the differences in toxicity outcomes between the treatment platforms.

Body mass index (BMI) has been associated with length of stay and post-operative complications; however, minimally invasive surgery has been proposed to mitigate this. Using real-world data of patients undergoing minimally invasive surgery for uterine cancer, we investigated the association between BMI and length of stay. Among patients discharged the same day, we explored post-operative complications associated with BMI. This was a National Surgical Quality Improvement Program retrospective cohort study including patients who underwent minimally invasive surgery for uterine cancer from 2013 to 2022. We performed a multi-variable Poisson regression to assess the association between BMI and length of stay, adjusting for a priori selected patient-level factors. In patients discharged the same day after surgery, we performed multi-variable linear regression to assess associations between BMI and the following post-operative complications: wound disruption, blood transfusion, surgical site infections, urinary tract infection, pneumonia, sepsis, deep vein thrombosis, pulmonary embolism, renal insufficiency, myocardial infarction, stroke/cerebrovascular accident, and re-admission, return to the operating room, and death within 30 days. A total of 33,307 patients were included. Their median BMI was 34.2 kg/m2 (interquartile range [IQR] 12.88) and median length of stay was 1 day (IQR 1). Length of stay increased by approximately 0.5 hours per 5 kg/m2 (per BMI obesity class categorization). In total, 9186 patients (27.6%) were discharged the same day after their minimally invasive surgery for uterine cancer, and in this cohort, no association between BMI and any post-operative complications were found. In patients undergoing minimally invasive surgery for uterine cancer, BMI was not associated with a clinically significant increase in length of stay, and in those discharged the same day, BMI was not associated with post-operative complications. Minimally invasive surgery for uterine cancer should be considered standard of care regardless of patient BMI, and same-day discharge for patients with elevated BMI is safe.

Acute kidney injury (AKI) is a known immune-related adverse event of cancer immune checkpoint inhibitor (ICI) therapy. Further population-based data on AKI incidence, risk factors and practice patterns post-ICI therapy are needed. We measured the cumulative incidence of AKI among advanced cancer patients while receiving ICI therapy and non-ICI systemic therapy in Ontario, Canada (2012-18). An increase in serum creatinine was used to define AKI and graded according to event severity. Time to event modeling was used to compare the risk of developing AKI, pre-disposing factors and survival outcomes. We studied 16 425 patients with advanced cancer receiving either ICI or non-ICI systemic therapy. Among 4380 patients receiving ICI therapy, the overall crude 4-year incidence of AKI (any stage) was 29% and severe AKI (stage ≥2) was 7%. Characteristics associated with a higher risk of AKI included male sex, genitourinary (versus other) malignancy, the presence of hypertension, diabetes or chronic kidney disease, and prescription of a non-steroidal anti-inflammatory drug. The risk of experiencing AKI was significantly lower among patients treated with ICI versus non-ICI systemic therapy [adjusted hazards ratio (aHR) 0.80, 95% confidence interval (CI) 0.74-0.86, P-value <.0001]. Among the 587 patients who experienced an AKI and were both alive and discontinued ICI therapy within 30days, 54 (9%) were re-challenged with ICI in the following 6months and 24 (44%) had a recurrent AKI event. Patients who were re-challenged with ICI therapy had improved overall survival as compared with patients that received other non-ICI systemic therapy (aHR 0.38, 95% CI 0.22-0.67, P-value <.001). Our real-world study demonstrates a modest risk for severe AKI among cancer patients receiving ICI therapy, lower than with exposure to other systemic cancer therapies. Among patients who developed AKI and stopped ICI therapy, re-challenge was uncommon but may warrant consideration for select patients.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs characterized by a covalently closed-loop structure. Although initially regarded as splicing byproducts, circRNAs are now recognized as essential regulators of gene and protein expression and play important roles in various human diseases. In recent years, growing evidence has indicated that a subset of circRNAs can be translated through cap-independent mechanisms to produce bioactive peptides or proteins. These findings expand the functional scope of circRNAs and offer new opportunities for RNA therapy. This review summarizes recent advances in circRNA biology, with an emphasis on their potential in diagnosis and treatment. We also review the therapeutic strategies targeting circRNAs at both the RNA and protein levels and the delivery systems that support circRNA-directed therapies. After we discuss how circRNA therapeutics may be integrated into precision medicine, we further highlight the current clinical progress and key challenges for advancing circRNA-based therapies toward clinical application.