Abstract
Objective
Programmed cell death-1 antibody therapy has demonstrated improved progression-free survival and overall survival in patients with metastatic renal cell carcinoma. However, there ...are limited studies on biomarkers that can predict the efficacy of immune checkpoint inhibitors. We examined the influence of peripheral inflammatory biomarkers on the clinical outcomes of patients with metastatic renal cell carcinoma treated with nivolumab.
Methods
Data of 38 patients with metastatic renal cell carcinoma, who were treated with nivolumab monotherapy after receiving at least one molecular targeted therapy from November 2016 to February 2021, were retrospectively reviewed and analyzed.
Results
Median progression-free survival and overall survival were significantly shorter in patients with low absolute lymphocyte count (<1300/μl) versus those with high absolute lymphocyte count (progression-free survival: P = 0.0102; overall survival: P = 0.0026). Median overall survival was shorter in patients with high neutrophil–lymphocyte ratio (≥3.0) versus those with low neutrophil–lymphocyte ratio (P = 0.0344). Multivariate analysis showed that absolute lymphocyte count was an independent factor for progression-free survival (hazard ratio = 2.332, 95% confidence interval = 1.012–5.375, P = 0.0468) and overall survival (hazard ratio = 4.153, 95% confidence interval = 1.108–15.570, P = 0.0347). Increased absolute lymphocyte count, 1 month after nivolumab initiation, was a positive predictive factor for progression-free survival (hazard ratio = 0.419, 95% confidence interval = 0.189–0.926, P = 0.0317) and overall survival (hazard ratio = 0.285, 95% confidence interval = 0.091–0.890, P = 0.0308).
Conclusion
Our study indicates that peripheral absolute lymphocyte count, before nivolumab initiation, is a predictor of poor response in metastatic renal cell carcinoma. Additionally, increased absolute lymphocyte count, 1 month post-nivolumab initiation, can be a predictor of the effects of nivolumab.
Peripheral absolute lymphocyte count, before nivolumab initiation, is an independent predictor of survival in metastatic renal cell carcinoma. Increased absolute lymphocyte count after initiation can be a predictor of nivolumab efficacy.
Abstract
Background
Immune checkpoint inhibitors cause various immune-related adverse events. The present study examined the association between the incidence of immune-related adverse events and ...survival outcomes in patients treated with nivolumab plus ipilimumab for patients with advanced renal cell carcinoma. In addition, we compared the effect of adverse event profiles on survival for patients receiving nivolumab plus ipilimumab.
Methods
A total of 35 patients with advanced renal cell carcinoma who were treated with nivolumab plus ipilimumab from August 2018 to August 2021 were retrospectively reviewed and analyzed. Cox proportional hazards models were used for univariate and multivariate analyses, and hazard ratio and 95% confidence intervals were calculated.
Results
Of the 35 patients, 22 (62.9%) experienced immune-related adverse events. The median progression-free survival (P = 0.0012) and overall survival (P = 0.0147) were significantly longer in patients with immune-related adverse events than in those without immune-related adverse events. Multivariate analysis showed that the incidence of immune-related adverse events was an independent factor for progression-free survival (hazard ratio = 4.940, 95% confidence interval: 1.558–15.664, P = 0.0067). Skin reaction was a positive predictive immune-related adverse events for progression-free survival (hazard ratio = 9.322, 95% confidence interval: 1.954–44.475, P = 0.0051).
Conclusion
Patients with advanced renal cell carcinoma with immune-related adverse events had superior clinical outcomes of nivolumab plus ipilimumab treatment than those without immune-related adverse events. Skin immune-related adverse events may be effective biomarkers in patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab.
Advanced renal cell carcinoma patients with immune-related adverse events treated with nivolumab plus ipilimumab had superior clinical outcomes. Skin immune-related adverse events may be effective biomarkers for nivolumab plus ipilimumab.
Introduction
Regressed germ cell tumors are a rare disease commonly diagnosed with metastatic symptoms without local symptoms in the testis.
Case presentation
A 33‐year‐old man with azoospermia was ...referred to our hospital. His right testis was slightly swollen, and ultrasonography revealed hypoechogenicity of the right testis with decreased blood flow. Right high orchiectomy was performed. Pathologically, the seminiferous tubules were absent or highly atrophied with vitrification degeneration; however, no neoplastic lesion was confirmed. One‐month post‐surgery, the patient noticed a mass in the left supraclavicular fossa, of which a biopsy revealed seminoma. The patient was diagnosed with a regressed germ cell tumor and underwent systemic chemotherapy.
Conclusion
We reported the first case of a regressed germ cell tumor discovered due to complaints of azoospermia.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Immuno-oncology (IO) combination therapy is the first-line treatment for advanced renal cell carcinoma (RCC). However, biomarkers for predicting the response to IO combination therapy are lacking. ...Here, we investigated the association between the expression of soluble immune checkpoint molecules and the therapeutic efficacy of IO combination therapy in advanced RCC. The expression of soluble programmed cell death-1 (sPD-1), soluble programmed cell death ligand-1 (sPD-L1), soluble PD-L2 (sPD-L2), and lymphocyte activation gene-3 (sLAG-3) was assessed in plasma samples from 42 patients with advanced RCC who received first-line IO combination therapy. All IMDC risk classifications were represented among the patients, including 14.3, 57.1, and 28.6% with favorable, intermediate, and poor risk, respectively. Univariate analysis revealed that prior nephrectomy, sPD-L2 levels, and sLAG-3 levels were significant factors affecting progression-free survival (PFS), whereas multivariate analyses suggested that sPD-L2 and sLAG-3 levels were independent prognostic factors for PFS. In a univariate analysis of the overall survival, prior nephrectomy and sPD-L2 levels were significant factors; no significant differences were observed in the multivariate analysis. No significant correlation was observed between the sPD-L2 and sLAG-3 levels and PD-L2 and LAG-3 expression via immunohistochemistry. In conclusion, sPD-L2 and sLAG-3 expression may serve as a potential biomarker for predicting IO combination therapy efficacy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
To investigate prognostic factors for patients with advanced renal cell carcinoma (RCC) treated with axitinib as second-line therapy.
This study included 35 patients with RCC who received axitinib as ...second-line therapy after the failure of first-line tyrosine kinases inhibitor from November 2012 to March 2017.
In univariate analyses, the following factors were associated with poor prognosis: bone and extrapulmonary metastasis for progression-free survival; and prior nephrectomy, Memorial Sloan Kettering Cancer Center risk classification, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification of poor, extrapulmonary metastasis and early tumor response for overall survival. Multivariate analyses identified the following factors as independent poor prognostic effects: extrapulmonary metastasis for progression-free survival, and no prior nephrectomy, IMDC risk classification of poor and extrapulmonary metastasis for overall survival.
Axitinib as second-line treatment is effective for patients with pulmonary metastasis alone of RCC, but not for those with extrapulmonary metastasis.
To analyze the risks and survival outcomes of non-definitive therapy (nDT) for muscle-invasive bladder cancer (MIBC), which may provide useful information for future treatment selection, the present ...study analyzed 124 patients who were diagnosed with MIBC (cT2-4aN1-2M0) and treated at Kurume University Hospital (Kurume, Japan) with definitive therapy (DT; including radical cystectomy and trimodal therapy) or nDT transurethral resection of bladder tumor (TURBT) monotherapy or TURBT plus chemotherapy. Differences in survival outcomes between the two groups were estimated using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards regression models were used for multivariate analysis of each survival outcome. Of the 124 patients, 45% were treated with nDT, and among these, 50% were treated with TURBT monotherapy and 50% were treated with TURBT plus chemotherapy. Of the patients who chose definitive treatment, 69% were treated with radical cystectomy. The median age in the nDT group was 77 years, which was significantly higher than that in the DT group. Additionally, the proportion of patients with poor performance status, high Charlson comorbidity index and high neutrophil-lymphocyte ratio values was significantly higher in the nDT group. nDT was associated with significantly reduced overall survival, cancer-specific survival and progression-free survival rates, and was a poor prognostic factor for all survival outcomes compared with DT. In conclusion, nDT was associated with a high cancer-related mortality risk. The most appropriate treatment method should be discussed with the patients after providing them with sufficient information on the risks and benefts of each treatment method.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with ...various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS:
= 0.0095; OS:
= 0.0182). Multivariate analysis suggested that prior nephrectomy hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359,
= 0.0075 and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648,
= 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (
< 0.0001) and OS (
= 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.
Introduction
We present tri‐modality therapy with i‐125 brachytherapy for high‐risk prostate cancer after holmium laser enucleation of the prostate.
Case presentation
A 75‐year‐old man had visited ...our hospital with complaints of dysuria. Holmium laser enucleation of the prostate was performed for benign prostatic hyperplasia. The resected histopathological prostate tissue showed malignancy (Gleason score: 3 + 3 = 6). Two years thereafter, Gleason score progressed (4 + 5 = 9) concomitantly with increased prostate‐specific antigen levels. Therefore, tri‐modality therapy, including brachytherapy, was applied. Combined androgen blockade therapy was conducted over a 9‐month period. One month after brachytherapy, external beam radiation was performed.
Conclusion
Brachytherapy following transurethral prostate surgery is relatively contraindicated because of increased adverse urethral event frequency and seed placement difficulties. A tri‐modality therapy, including brachytherapy, was implemented without any major problems in this patient with high‐risk prostate cancer after holmium laser enucleation of the prostate, following which he had a favorable prognosis without recurrence for 6 years.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To evaluate the oncological outcomes and genitourinary and gastrointestinal adverse events in acute and late-phases of iodine-125 low-dose-rate brachytherapy for localized prostate cancer.
We ...retrospectively evaluated 334 patients treated for localized prostate cancer with low-dose-rate brachytherapy. Bio-chemical relapse-free survival, cause-specific survival, and overall survival were evaluated using Kaplan-Meier method and log-rank test. Incidence of adverse events was calculated using National Cancer Institute common terminology criteria for adverse events, version 5. Logistic regression was used to identify independent predictors of acute and late-phase genitourinary and gastrointestinal adverse events.
National Comprehensive Cancer Network's low-, intermediate-, and high-risk groups included 133 (39.8%), 163 (48.8%), and 38 (11.3%) patients, respectively. The 5-year cause-specific survival rate was 100%. The 5-year bio-chemical relapse-free survival rates for the low-, intermediate-, and high-risk groups were 98.3%, 95.8%, and 100%, respectively. One patient had a ≥ grade 3 acute adverse event. The 5-year cumulative ≥ grade 1, ≥ grade 2, and ≥ grade 3 genitourinary adverse event rates were 27.9%, 14.4%, and 0.5%, respectively. The 5-year cumulative ≥ grade 1, ≥ grade 2, and ≥ grade 3 gastrointestinal adverse event rates were 3.1%, 1.5%, and 0.5%, respectively. A high pre-treatment international prostate symptom score and non-use of α1-blockers were associated with an increased risk of acute genitourinary adverse events.
Low-dose-rate brachytherapy had good oncological outcomes, with acceptable adverse event rates. Pre-treatment urinary function and use of α1-blockers may be useful in predicting and preventing acute genitourinary adverse events.
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IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK
We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING) with overexpression of glomerular advanced glycation end products (AGEs) and their receptor (RAGE). A 59-year-old ...Japanese man with nephrotic syndrome, who had a smoking history of one pack of cigarettes per day for approximately 40 years, presented with a 3-year history of urinalysis abnormalities without clinical evidence of diabetic mellitus. The patient’s leg edema progressively worsened over the previous 2 years, and he was admitted to our hospital. Renal biopsy showed mesangial expansion with diabetic Kimmelstiel–Wilson-like nodular lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron microscopy. Skin AGE level measured using AGE reader was higher in this case than the average level in age-matched Caucasians. In addition, immunohistochemical analysis revealed that
N
-carboxymethyl lysine, one of the major AGEs, and RAGE were overexpressed and podocin expression was decreased in the peripheral area of the glomerular nodular lesions. These observations suggest that AGEs–RAGE system may be activated in smoking-related ING, possibly leading to the progression of renal dysfunction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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