Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes.

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Efficacy and safety of the enzymatic mixture - Lipase, collagenase and hyaluronidase - In the treatment of moderate to severe submental fat: A prospective cohort study.

Purpose: To study the effect of the enzymatic mixture: Lipase, Collagenase and Hyaluronidase in the treatment of submental fat. Methods: A monocentric prospective cohort study including 10 female patients, aged between 18 and 65 years old, who received treatment for submental fat with a mixture of Lipase, Collagenase, and Hyaluronidase. The treatment protocol consisted of one treatment session every 21 days for a total of 3 sessions. In each session, 4 ml of the enzymatic mixture (1 ml of Collagenase GH PB20, 1 ml of Hyaluronidase PB 3000 and 2 ml of Lipase PB 500) + 2 ml of Lidocaine 2% were injected in the submental fat (SMF). Efficacy was assessed four weeks after the last session. Co-Primary Outcome was defined as the improvement of ≥ 1-point in Clinician-Reported and Patient-Reported Sub-mental Fat Rating Scales (CR-SMFRS and PR-SMFRS). Secondary Outcomes included score reductions in Patient-Reported Sub-mental Fat Impact Scale (PR-SMFIS), ≥10% reduction in submental fat pad thickness by ultrasound, and Subject Self-Rating Scale (SSRS) responses of 4, 5, or 6. Results: The Co-Primary outcome was achieved in 9 out of 10 patients. A considerable reduction of 22.8% in the PR-SMFIS was observed. Furthermore, 9 out of 10 patients expressed overall satisfaction with the treatment. Submental fat reduction of more than 10% was observed in 9 out of 10 patients in neutral position and in all patients in flexed position. Adverse effects were only limited to local reactions. Conclusion: The enzymatic mixture of Lipase, Collagenase and Hyaluronidase is an effective and safe minimally-invasive method for the reduction of SMF that can be used alone or in conjunction with other treatment modalities.

Update on Biomarkers in Renal Cell Carcinoma.

Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.

Clinicodemographic characteristics of extraosseous ewing sarcoma: A comparative meta-analysis of pediatric and adult patients.

Background: Evidence suggests different presentation patterns and prognosis of extraosseous Ewing Sarcoma (EES) based on age. Thus, we carried out this study to test the difference between children and adult EES cases regarding clinicodemographic characteristics and prognosis. Methods: A total of 4 databases were explored yielding 18 relevant studies for data synthesis. Outcomes included the comparison of demographic and clinical characteristics as well as prognosis between children and adults with EES. Log odds ratio (logOR) and its 95% confidence interval (CI) were pooled across studies. Statistical models/methods were selected based on heterogeneity. Results: Our analysis included a total of 1261 children and 1256 adults. When we compared these two age categories, we did not observe a significant difference in the risk of developing EES [logOR = -0.13; 95% CI: -0.65: 0.39; I2 = 88.42%]. No significant differences regarding gender, tumor location, and size (≤5 vs. >5 cm), EWSR1 positivity, or management modality. We did not observe significant difference regarding clinical outcomes, such as 5-year overall survival and event-free survival, recurrence, mortality, no evidence of disease, and secondary metastasis. Conclusions: Our findings highlight the absence of an association between the age category of patients and the incidence of EES, as well as its clinical outcomes.

Emerging Biomarkers of Response to Systemic Therapies in Metastatic Clear Cell Renal Cell Carcinoma.

Patients with metastatic clear cell renal cell carcinoma (mccRCC) experience highly heterogeneous outcomes when treated with standard-of-care systemic regimens. Therefore, valid biomarkers are needed to predict the clinical response to these therapies and help guide management. In this review, the authors outline relevant and promising biomarkers for patients with mccRCC receiving systemic therapies, with a focus on immunotherapy-based regimens.

Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes.

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory stimuli that maintain immunosuppression ("brakes") and priming the immune system to target tumoral cells ("gas pedals"). We explore each class of novel immunotherapy, including the rationale behind it, supporting preclinical and clinical evidence, and limitations.

Novel Targeted Therapies for Renal Cell Carcinoma: Building on the Successes of Vascular Endothelial Growth Factor and mTOR Inhibition.

Targeted therapies have revolutionized the treatment of renal cell carcinoma (RCC). The VHL/HIF pathway is responsible for the regulation of oxygen homeostasis and is frequently altered in RCC. Targeting this pathway as well as the mTOR pathway have yielded remarkable advances in the treatment of RCC. Here, we review the most promising novel targeted therapies for the treatment of RCC, including HIF2α, MET, metabolic targeting, and epigenomic reprogramming.

Phenotype Prevalence and Health-Related Quality of Life of Lebanese Women With Polycystic Ovary Syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Our study aimed to assess, for the first time, the phenotype prevalence and the health-related quality of life of Lebanese women with PCOS. METHODS: This was a cross-sectional study conducted on 322 Lebanese women with PCOS, using a questionnaire containing sociodemographic data, comorbidities, disease-related clinical questions, and the validated PCOS questionnaire (PCOSQ). The quality of life mean scores and phenotypes were compared and correlated among the different sociodemographic data, comorbidities, and disease-related questions. RESULTS: Phenotype A (67%) was the most common phenotype. High waist circumference and higher Body Mass Index (BMI) were reported mostly in classic phenotypes in comparison with nonclassic (P < .05). The mean total score of all PCOSQ domains was 3.61 ± 1.60. The mean score for each domain (from the greatest to the least serious concern) was menstrual problems (3.31 ± 1.26), emotion (3.33 ± 1.22), weight (3.41 ± 2.12), body hair (3.86 ± 1.79), and infertility (4.15 ± 1.61). Age was negatively correlated only to weight domain score (r = -0.17, P = .002). BMI was associated only with emotion and weight domain scores (P = .017 and P < .001, respectively). A bigger impairment in nearly all subscales of the PCOSQ in patients presenting with abdominal obesity, glucose intolerance, and increased blood pressure was noted (P < .05). CONCLUSION: Most Lebanese women with PCOS present phenotype A and have a serious impairment in their health-related quality of life, particularly in the menstrual and emotional domains. This highlights the need for community and individual support.

Spinopelvic Adaptations in Standing and Sitting Positions in Patients With Adult Spinal Deformity.

Purpose To describe spinopelvic adaptations in the standing and sitting positions in patients with adult spinal deformity (ASD). Methods Ninety-five patients with ASD and 32 controls completed health-related quality of life (HRQOL) questionnaires: short form 36 (SF36), Oswestry Disability Index (ODI), and visual analog scale (VAS) for pain. They underwent biplanar radiography in both standing and sitting positions. Patients with ASD were divided into ASD-front (frontal deformity Cobb > 20°, n = 24), ASD-sag (sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT) > 25°, or pelvic incidence (PI)-lumbar lordosis (LL) > 10°, n = 40), and ASD-hyper thoracic kyphosis (TK >60°, n = 31) groups. Flexibility was defined as the difference (Δ) in radiographic parameters between the standing and sitting positions. The radiographic parameters were compared between the groups. Correlations between HRQOL scores were evaluated. Results All participants increased their SVA from standing to sitting (ΔSVA<0), except for patients with ASD-sag, who tended to decrease their SVA (78-62 mm) and maximize their pelvic retroversion (27-40° vs 10-34° in controls, p<0.001). They also showed reduced thoracic and lumbar flexibility (ΔLL = 3.4 vs 37.1°; ΔTK = -1.7 vs 9.4° in controls, p<0.001). ASD-hyperTK showed a decreased PT while sitting (28.9 vs 34.4° in controls, p<0.001); they tended to decrease their LL and TK but could not reach values for controls (ΔLL = 22.8 vs 37.1° and ΔTK = 5.2 vs 9.4°, p<0.001). The ASD-front had normal standing and sitting postures. ΔSVA and ΔLL were negatively correlated with the physical component scale (PCS of SF36) and ODI (r = -0.39 and r = -0.46, respectively). Conclusion Patients with ASD present with different spinopelvic postures and adaptations from standing to sitting positions, with those having sagittal malalignment most affected. In addition, changes in standing and sitting postures were related to HRQOL outcomes. Therefore, surgeons should consider patient sitting adaptations in surgical planning and spinal fusion. Future studies on ASD should evaluate whether physical therapy or spinal surgery can improve sitting posture and QOL, especially for those with high SVA or PT.

Reliability assessment of cervical spine parameters measured on full-body radiographs in asymptomatic subjects and patients with spinal deformity.

BACKGROUND: Cervical spinal alignment is usually assessed on full-body radiographs allowing for the concomitant evaluation of possible compensatory mechanisms that may occur at any level in the setting of postural malalignment. HYPOTHESIS: Cervical parameters measured on full-body radiographs are reliable. PATIENTS AND METHODS: A total of 70 subjects were included and divided in 3 groups: asymptomatic adults (n=21), adolescents with idiopathic scoliosis (n=20), and adults with spinal deformity (n=29), for whom full-body low-dose biplanar radiographs were obtained. Eighteen cervical parameters including gaze and cervical curvature, upper cervical spine, global cervical alignment, thoraco-cervical and cervico-pelvic parameters were measured by 4 operators, three times each. The intraclass correlation coefficient (ICC) and the 95% confidence interval (95% CI) where calculated for each parameter and compared between the 3 groups. RESULTS: ICC and the 95% CI were similar between the 3 groups. The measured parameters showed a very high repeatability (ICC>0.8) except for C0-C2, which presented an average repeatability (ICC=0.57). The cSVA, CTPA, C2-SPi, cranial offset, T1-SPi, CBVA and cranial tilt had a 95% CI<2 (° or cm). The TIA, T1-CL and C0-C2 had a 95% CI>6°. DISCUSSION: The poor visibility of the foramen magnum, hard palate, C7, T1, and the sternum on radiographs could explain why certain parameters showed a higher measurement error. The assessment of these error margins is essential for an accurate evaluation of cervical spinal deformities and a proper therapeutic approach. LEVEL OF EVIDENCE: III; retrospective analysis of prospectively collected data.