Impact of Postoperative Bracing Following Spinal Fusion for Degenerative Lumbar Conditions: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is a lack of consensus on the use of postoperative bracing for lumbar degenerative conditions. Spine surgeons typically determine whether to apply postoperative braces based primarily on clinical experience rather than robust, evidence-based medical data. Thus, the present study sought to assess the impact of postoperative bracing on clinical outcomes, complications, and fusion rates following lumbar fusion surgery in patients with degenerative spinal conditions. METHODS: Only randomized controlled studies published between January 1990 and 20 October 2023 were included in this meta-analysis. The primary outcome measures consisted of pre- and postoperative assessments of the Oswestry Disability Index (ODI) and visual analog scale (VAS) scores. Improvements in VAS and ODI scores were analyzed in the early postoperative period (1 month after operation) and at final follow-up, respectively. The analysis also encompassed fusion rates and complications. RESULTS: Five studies with 362 patients were included in the present meta-analysis. In the early postoperative period, the brace group showed a relatively better improvement in ODI scores compared with the no-brace group (19.47 vs 18.18), although this difference was not statistically significant (P = 0.34). Similarly, during the late postoperative period, the brace group demonstrated a slightly greater improvement in VAS scores in comparison to the no-brace group (4.05 vs 3.84), but this difference did not reach statistical significance (P = 0.30). The complication rate was relatively lower in the brace group compared with the no-brace group (14.9% vs 17.4%), although there was no statistical difference between the 2 groups (P = 0.83). Importantly, there were no substantial differences in fusion rates between patients with or without braces. CONCLUSION: The present meta-analysis revealed that the implementation of a brace following lumbar fusion surgery did not yield substantial differences in terms of postoperative pain relief, functional recovery, complication rates, or fusion rates when compared with cases where no brace was employed. CLINICAL RELEVANCE: This meta-analysis provides valuable insights into the clinical impact of postoperative bracing following lumbar fusion surgery for degenerative spinal conditions.

Comparative outcomes of obese and non-obese patients with lumbar disc herniation receiving full endoscopic transforaminal discectomy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the impact of full endoscopic transforaminal discectomy (FETD) on clinical outcomes and complications in both obese and non-obese patients presenting with lumbar disc herniation (LDH). METHODS: A systematic search of relevant literature was conducted across various primary databases until November 18, 2023. Operative time and hospitalization were evaluated. Clinical outcomes included preoperative and postoperative assessments of the Oswestry Disability Index (ODI) and visual analogue scale (VAS) scores, conducted to delineate improvements at 3 months postoperatively and during the final follow-up, respectively. Complications were also documented. RESULTS: Four retrospective studies meeting inclusion criteria provided a collective cohort of 258 patients. Obese patients undergoing FETD experienced significantly longer operative times compared to non-obese counterparts (P = 0.0003). Conversely, no statistically significant differences (P > 0.05) were observed in hospitalization duration, improvement of VAS for back and leg pain scores at 3 months postoperatively and final follow-up, improvement of ODI at 3 months postoperatively and final follow-up. Furthermore, the overall rate of postoperative complications was higher in the obese group (P = 0.02). The obese group demonstrated a total incidence of complications of 17.17%, notably higher than the lower rate of 9.43% observed in the non-obese group. CONCLUSION: The utilization of FETD for managing LDH in individuals with obesity is associated with prolonged operative times and a higher total complication rate compared to their non-obese counterparts. Nevertheless, it remains a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity.

Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. METHODS: A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. RESULTS: The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. CONCLUSION: Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.

Safety and Efficacy of Second-Line TKI Plus Anti-PD1 in Metastatic Non-Clear Cell Renal Cell Carcinoma: A Real-World Study.

OBJECTIVES: Guidelines recommend clinical trials or tyrosine kinase inhibitor (TKI) as the first-line option for systemic therapy for non-clear cell renal cell carcinoma (nccRCC) with limited efficacy. However, the preferred subsequent options remain unclear when patients progress after first-line treatment. This study aimed to evaluate the efficacy and safety of anti-PD-1 plus TKI therapy as the second-line regimen in nccRCC. PATIENTS AND METHODS: We conducted a retrospective analysis of patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020. The baseline characteristics of the patients and adverse events (AEs) were collected. Efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). RESULTS: The current study enrolled 65 patients, with a median age of 48 (interquartile 37-60) years. Among all patients, 21 received TKI monotherapy while 44 patients received combination therapy (TKI plus anti-PD1). The ORR and DCR for the whole cohort were 38.5% and 56.9%, respectively. ORR (50.0% vs. 14.3%, P = .006) and DCR (70.5% vs. 28.6%, P = .001) were improved in the combination group compared with the TKI group. The overall second-line PFS was 7.7 (95% CI: 6.1-9.3) months and OS was 25.2 (19.5-30.8) months. Patients receiving combination therapy had a longer PFS compared with those receiving TKI monotherapy [median PFS (95% CI): 9.2 (5.9-12.4) vs. 5.4 (2.6-8.2) m, Log-rank P = .002]. The incidence of treatment-related AEs of grade 3 or higher was comparable between the 2 groups (56.8% vs. 52.4%). CONCLUSION: Anti-PD-1 plus TKI therapy appeared effective and safe in the treatment of patients with metastatic nccRCC who progressed after first-line TKIs.

CXCL14 as a potential marker for immunotherapy response prediction in renal cell carcinoma.

Background: Epigenetic mechanisms play vital roles in the activation, differentiation, and effector function of immune cells. The breast and kidney-expressed chemokine (CXCL14) mainly contributes to the regulation of immune cells. However, its role in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in renal cell carcinoma (RCC). Objectives: This study aimed to elucidate the role of CXCL14 in predicting the efficacy of immunotherapy in patients with RCC. Methods: CXCL14 expression and RNA-sequencing, single-cell RNA-sequencing (scRNA-seq), and survival datasets of RCC from public databases were analyzed, and survival was compared between different CXCL14 levels. The correlation between CXCL14 and immune infiltration and human leukocyte antigen (HLA) gene expression was analyzed with TIMER2.0 and gene expression profiling interactive analysis. Institutional scRNA-seq and immunohistochemical staining analyses were used to verify the relationship between CXCL14 expression level and the efficacy of immunotherapy. Results: CXCL14 was expressed in fibroblast and malignant cells in RCC, and higher expression was associated with better survival. Enrichment analysis revealed that CXCL14 is involved in immune activation, primarily in antigen procession, antigen presentation, and major histocompatibility complex assemble. CXCL14 expression was positively correlated with T-cell infiltration as well as HLA-related gene expression. Among the RCC cohort receiving nivolumab in Checkmate 025, the patients with CXCL14 high expression had better overall survival than those with CXCL14 low expression after immunotherapy. scRNA-seq revealed a cluster of CXCL14+ fibroblast in immunotherapy responders. Immunohistochemistry analysis verified that the patients with high CXCL14 expression had an increased proportion of high CD8 expression simultaneously. The expression level of CXCL14 was associated with CXCR4 expression in RCC. Conclusion: CXCL14 expression is associated with immunotherapy response in RCC. It is a promising biomarker for immunotherapy response prediction and may be an effective epigenetic modulator in combination with immunotherapy approaches.

CXCL14 as potential predictor for immunotherapy response in kidney cancer Kidney-expressed chemokine (CXCL14) regulates immune cells. We studied how it affects the body's immune response to kidney cancer based on public and private database and staining. We found that higher levels of CXCL14 in kidney cancer were linked to better patient survival. CXCL14 seems to help activate the immune system. When patients with high CXCL14 levels received immunotherapy, they tended to survive longer than those with low levels. Fibroblasts with CXCL14 were present in patients responding to immunotherapy. Further tests confirmed that high CXCL14 levels were related to more immune cells. CXCR4 may be its receptor in kidney cancer. This suggests that measuring CXCL14 levels could help predict how well a patient might respond to immunotherapy for kidney cancer.

A critical review of adsorption isotherm models for aqueous contaminants: Curve characteristics, site energy distribution and common controversies.

The quantitative description of the equilibrium data by the isotherm models is an indispensable link in adsorption studies. The previous review papers focus on the underlying assumptions, fitting methods, error functions and practical applications of the isotherm models, usually ignoring their curve characteristics, selection criteria and common controversies. The main contents of this review include: (i) effect of the model parameters on the isotherm curves; (ii) determination of the site energy distribution; (iii) selection criteria of the isotherm models; and (iv) elimination of some common controversies. It is of great significance to reveal the curve characteristics for selecting a proper isotherm model. The site energy distribution is conducive to understanding the physicochemical properties of the adsorbent surface. The complete isotherm is recommended to be correlated with the experimental data. The model parameter qmax should be cautiously adopted for comparison of the adsorbent performance. The residual plot can be used to diagnose the fitting quality of the isotherm models further. This review also addresses some common mistakes and controversies and thereby avoids their propagation in future publications.

The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. RESULTS: We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8 + T cell infiltration in RCC tumor tissues. CONCLUSIONS: We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.

Special issue "The advance of solid tumor research in China": 68Ga-PSMA-11 PET/CT for evaluating primary and metastatic lesions in different histological subtypes of renal cell carcinoma.

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of 68 Ga-prostate specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) in the detection of primary and metastatic lesions in such patients. We retrospectively analyzed 50 RCC patients who underwent 68 Ga-PSMA-11 PET/CT from November 2017 to December 2020. We observed a higher median accuracy and tumor-to-background maximum standard uptake value (SUVmax ) ratio (TBR) of 68 Ga-PSMA-11 PET/CT in clear cell RCC (ccRCC; 96.57% and 6.00, respectively) than in non-clear cell RCC (ncRCC; 82.05% and 2.99, respectively). The accuracies in detecting lesions in the renal region, bone, lymph nodes and lungs in ccRCC were 100.00%, 95.00%, 98.08% and 75.00%, respectively, and those in the renal region, bone and lymph nodes in ncRCC were 100.00%, 86.67% and 36.36%, respectively. The median TBRs of the lesions from the above locations were 0.38, 10.96, 6.69 and 13.71, respectively, in ccRCC and 0.13, 4.02 and 0.73, respectively, in ncRCC. The PSMA score evaluated with immunohistochemistry was correlated with the SUVmax (P = .046) in RCC. Higher PSMA scores were observed in ccRCC than in ncRCC (P = .031). 68 Ga-PSMA-11 PET/CT resulted in changes in clinical management in 12.9% (4/31) of cases because of the discovery of new metastases not detected with conventional imaging. These results indicate that 68 Ga-PSMA-11 PET/CT is a promising method for the detection of metastatic lesions in ccRCC, especially for those in the bone and lymph nodes.

Prognostic value of JAK3 promoter methylation and mRNA expression in clear cell renal cell carcinoma.

INTRODUCTION: Janus kinase 3 (JAK3) is a well-established oncogene in clear cell renal cell carcinoma (ccRCC). The methylation status of oncogene promoters has emerged as biomarkers for cancer diagnosis and prognosis. OBJECTIVE: This study aims to investigate the biological and clinical significance of JAK3 promoter methylation in ccRCC. METHODS: We analyzed the relationship of JAK3 promoter methylation with its mRNA expression, overall survival, and immune cell infiltration in a cohort obtained from The Cancer Genome Atlas (TCGA), which was further validated by another independent cohort. We further validated correlations of JAK3 promoter methylation with JAK3 expression, overall survival, and immune cell infiltration in an independent ccRCC cohort (Sun Yat-sen University Cancer Center (SYSUCC) cohort) by methods of immunohistochemistry (IHC) and pyrosequencing. RESULTS: We found JAK3 promoter was significantly hypomethylated in tumor tissues compared to normal adjacent tissues in ccRCC, and JAK3 promoter hypomethylation was strongly correlated with high JAK3 mRNA expression in all three ccRCC cohorts we examined. JAK3 promoter hypomethylation predicted advanced clinicopathological characteristics and shorter overall survival (TCGA cohort and SYSUCC cohort). Furthermore, we found that JAK3 promoter methylation was significantly associated with immune cell infiltration and expression of immune checkpoint molecules (TCGA cohort and CPTAC cohort). Finally, our SYSUCC cohort validated that JAK3 promoter methylation was correlated with CD4+ and CD8+ T cell infiltration in ccRCC tumor tissues. CONCLUSION: Our data demonstrated that the crucial role of JAK3 promoter methylation in its expression regulation and tumor microenvironment. JAK3 promoter methylation and expression are associated with clinicopathological characteristics, overall survival, and immune cell infiltration in ccRCC. We propose a rationale for further validation of JAK3 promoter methylation as a molecular biomarker for predicting responses to immune checkpoint inhibitors in ccRCC.

Genomic Characteristics and Single-Cell Profiles After Immunotherapy in Fumarate Hydratase-Deficient Renal Cell Carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FHRCC) is highly malignant, but the urgent need for effective treatment remains unmet. We aimed to analyze the genomic characteristics and microenvironment of FHRCC and the cause of heterogeneous response to immune checkpoint inhibitor (ICI)-based treatment at single-cell level. EXPERIMENTAL DESIGN: Whole-exome sequencing and IHC staining analyses were performed in 30 advanced FHRCC patients. Single-cell RNA sequencing following ICI-based treatment was conducted in 4 patients. The clinical characteristics, therapeutic effect, and follow-up data were analyzed. RESULTS: The median tumor mutation burden was only 0.14 mutations per megabase. IHC staining showed an immune-active tumor microenvironment characterized by extensive CD8+ T-cell infiltration. ATM expression was inversely correlated with percentage of tumor-infiltrating CD8+ T cells. Trajectory analysis indicated gradually upregulated exhausted markers and an increased apoptotic trend of CD8+ T cells despite continuous exposure to ICI-based treatment. ICI-based treatment was associated with improved overall response rate (17.6% vs. 0%, P = 0.046) and disease control rate (DCR; 64.7% vs. 12.5%, P = 0.004) compared with tyrosine kinase inhibitor. Among patients with germline mutation, the ORR (16.7% vs. 0%, P = 0.086) and the DCR (66.7% vs. 14.3%, P = 0.011) were higher after ICI-based treatment. CONCLUSIONS: Immune infiltration is frequent in FHRCC. ICI-based treatment is a promising regimen, and treatment response depends on the functional status of tumor-infiltrating lymphocytes. ICI-based treatment cannot reverse the exhaustion of CD8+ T cells in patients with progressive disease, highlighting the need for additional therapeutic strategies.

Locoregional recurrence after nephrectomy for localized renal cell carcinoma: Feasibility and outcomes of different treatment modalities.

BACKGROUND: Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC. MATERIALS AND METHODS: Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD-1 inhibitors) were divided into two groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method, Cox regression model. Patients were matched with propensity score matching. RESULTS: Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non-clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2-year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients. CONCLUSIONS: Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma.

BACKGROUND: Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models. RESULTS: Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0-1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07-0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06-0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group. CONCLUSIONS: Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone.

BACKGROUND: To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P). METHODS: Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety. RESULTS: One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS. CONCLUSIONS: A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.

Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: extent of tumor burden eradicated by radiotherapy.

PURPOSE: We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier method, Cox regression model and the Fine and Gray method. RESULT: A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0-1 (HR 0.389, 95% CI 0.167-0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108-0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0-1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions. CONCLUSION: Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized.

Survival After Combining Stereotactic Body Radiation Therapy and Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma.

BACKGROUND: Stereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs. METHODS: Data of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed. RESULTS: A total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P < 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10-3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25-4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26-0.65; P < 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31-0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P < 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities. CONCLUSIONS: Combining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk.

Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience.

BACKGROUND: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone. METHODS: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group). RESULTS: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05-0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37-5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01-0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09-0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06-0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03-0.57; P = 0.007) had improved OS with AbiRT. CONCLUSIONS: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.

Stereotactic body radiotherapy-induced abscopal effect twice after pembrolizumab failure in hereditary leiomyomatosis and renal cell carcinoma: a case report with genetic and immunologic analysis.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare but aggressive disease. Immune checkpoint inhibitors (ICIs) have been an indispensable component for the management of advanced renal cell carcinoma, and stereotactic body radiotherapy (SBRT) has offered additional immunological effect boost for improving the treatment outcomes of the patients. However, the synergistic effect of ICIs with SBRT in HLRCC remains largely unexplored. We present the case of a 34-year-old woman with advanced HLRCC who underwent radical nephrectomy but soon relapsed at the retroperitoneal lymph nodes (RPLN). She was prescribed sunitinib but still progressed on twenty cycles with bulky RPLN and ascites. She was then treated with axitinib and pembrolizumab for twenty months, and received SBRT for the progression of RPLN upon which the first abscopal effect was observed via significant shrinkage of in-field and out-field tumor lesions. Five months later, she underwent a second course of SBRT for pelvic mass progression and the second abscopal effect was observed. Genetic and immunologic characteristics revealed a large number of tumor-infiltrating immune cells and high levels of PD-L1 expression. This case report demonstrates the synergistic effect of ICIs and SBRT in HLRCC and the potential mechanism for the repeated SBRT-induced abscopal effect, supporting the application of SBRT to oligometastatic lesion during ICIs treatment to delay disease progression. Further studies are needed to verify the strategy of combining ICIs and SBRT in advanced HLRCC.