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The ASCO-GU 23 conference was held offline as scheduled after the pandemic. A total of 167 abstracts in the field of renal cell carcinoma has been posted during the conference, covering the first PET/CT diagnostic technology targeting tumors in renal cell carcinoma, risk stratified interpretation of the previous clinical trial results, and exploring the value of tumor and serum biomarkers for precise classification therapy, as well as providing evidence for the therapeutic scheme sequencing.
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Objective:To explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.
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Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.
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JS001 (toripalimab) is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1 (PD1). In this study, we used a different iodine isotype (I) to label JS001 probes to target the human PD1 (hPD1) antigen. , the half maximal effective concentration (EC) value of I-JS001 did not significantly differ from that of JS001. The uptake of I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation. The binding affinity of I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized C57BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography (immuno-PET) imaging. Pathological staining was used to assess the expression of PD1 in tumor tissues. The homologous Ihuman IgG (IhIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the I-JS001 group at different time points was significantly higher than that of the blocking group or the I-hIgG group in the humanized mouse model. Taken together, these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.
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Objective: To investigate the clinical characteristics, treatment methods, and prognosis of metastatic papillary renal cell car-cinoma (pRCC). Methods: The clinical data of metastatic pRCC patients treated at the Department of Kidney Cancer and Melanoma, Pe-king University Cancer Hospital, were retrospectively analyzed. The prognosis of these patients was stratified through international metastatic renal cell carcinoma database consortium (IMDC) model. Survival and influencing factors were further analyzed using the Kaplan-Meier method and Cox proportional risk regression model. Results: From January 2003 to March 2018, 93 patients (median age, 50.0 years) were diagnosed with metastatic pRCC: 89 (95.7%) typeⅡcases and 4 (4.3%) typeⅠcases. The median follow-up dura-tion was 23.1 months, with 90, 44, and 14 patients having received first-line, second-line, and third-line treatments, respectively. The median overall survival (OS) of the 93 patients was (31.5±5.9) months [95% confidence interval (CI): 19.9-43.1], while the median OS of patients with low-, intermediate-, and high-risk (classified as per the International Metastatic Renal Cell Carcinoma Database Con-sortium [IMDC]) were (100.0±32.8), (38.3±8.2), and (16.4±1.2) months, respectively (high-risk vs. low/intermediate-risk, P<0.001; low-risk vs. intermediate-risk, P=0.015). The median progression free survival (PFS) with first-line treatment was (6.6±0.5) months. And the median PFS of the corresponding three groups stratified by IMDC score were (17.5±5.7), (7.1±2.3), and (5.2±1.5) months, respectively (high-risk vs . low-risk, P=0.002; high-risk vs . intermediate-risk, P=0.01). Conclusions: Metastatic pRCC is noted to have unique biologi-cal characteristics. The IMDC model can be used to predict the efficacy of first-line treatment using tyrosine kinase inhibitors as well as the prognosis of metastatic papillary renal cell carcinoma in such patients.
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<p><b>OBJECTIVE</b>To investigate the efficacy and safety of sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) on a 2 weeks on/1 week off intermittent dosing schedule.</p><p><b>METHODS</b>A total of 11 mRCC patients were enrolled to receive sunitinib 50 mg/day in 2 weeks on/1 week off schedule per 6 weeks till disease progression or intolerable toxicity occurred. The primary end point was progression free survival (PFS), the secondary end points were overall survival (OS), incidence of adverse effects and objective response.</p><p><b>RESULTS</b>The objective response rate in the 11 cases was 45.5% and disease control rate 72.7% (partial response n = 5, stable disease n = 3). Till the last follow up on Dec 2013, the median PFS was 17.0 months (95% CI 7.3 to 26.7 months), and median OS 26.0 months (95% CI 2.2 to 49.8 months). The common adverse events included leucopenia, thrombocytopenia, diarrhea, mucositis and hand-foot skin reaction. Dose reduction to 37.5 mg was seen only in 2 patients without discontinuation.</p><p><b>CONCLUSIONS</b>Sunitinib on an intermittent dosing schedule 2 weeks on /1 week off as first-line therapy for mRCC patients shows a good efficacy and tolerance, with less grade 3-4 drug-related toxicities and a tendency of prolonged PFS in mRCC patients.</p>
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Therapeutic Uses , Carcinoma, Renal Cell , Drug Therapy , Disease-Free Survival , Drug Administration Schedule , Indoles , Pharmacology , Therapeutic Uses , Kidney Neoplasms , Drug Therapy , Pilot Projects , Pyrroles , Pharmacology , Therapeutic Uses , Treatment OutcomeABSTRACT
Objective To evaluate the efficacy and safety of sunitinib as first line treatment in patients with metastatic renal cell carcinoma (RCC). Methods This study included 46 Chinese patients who were diagnosed with metastatic RCC after radical nephrectomy. The patients received oral sunitinib (50 mg once daily on a 4 weeks on, 2 weeks off) on a 6 weeks cycle dose schedule until disease progression or intolerable toxicities occurred. Results The overall objective response rate was 32.6% (95% confidence interval [CI, 19.1% to 46. 1%]), and the disease control rate was 86.9%,with complete response (CR) 0 (0%), partial responses (PRs) 15 (32.6%), stable disease (SD) 25(54.3 %), and progression disease (PD) 6 ( 13. 1%). The median progression-free survival was 11 months, and the 1-year survival rate was 65.2%, while the median overall survival (mOS) has not been reached. The main adverse events included fatigue 33 (71.7%), skin discoloration 29 (63.0 %),anorexia 28 (60.9%), hand-foot syndrome 26 (56.5%), oral mucositis 25 (54.3%), hypertension 19 (41.3%), facial edema 18 (39.1%), diarrhea 17 (37.0%), hemorrhage 17 (37.0%), nausea 15 (32.6%), and hematological toxicity: leukopenia 32 (69.6%), neutropenia 30 (65.2%), thrombocytopenia 28 (60.9%), anemia 21 (45.7%). Most of grade 3/4 serious adverse events were thrombocytopenia in 15 (32. 6%) patients. Conclusions Sunitinib has a prominent effect in metastatic renal cell cancer in a Chinese population with mostly mild to moderate adverse reactions. More attention should be paid to grade 3/4 adverse reaction of thrombocytopenia.
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Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.
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Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.
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Objective To investigate the diagnostic significance of argyrophilic nuclear organizer regions(AgNORs) of peripheral T lymphocytes in elderly cancer patients. Methods AgNORs was examined using KL tumor image analysis system in 45 cases of health control,36 cases of elderly inflammatory patients,97 cases of elderly cancer patients and 30 cases of elderly tumor-cured patients. CD3,CD4,CD8,CD4/8 and NK were detected by flow cytometer in cancer patients. Results Compared with normal controls,inflammation and tumor-cured patients,AgNORs was decreased extremely in elderly patients with cancer. Moreover,AgNORs was decreased in tumor metastasis status. Conclusions In analyzed elderly cancer patient cases,the expression of AgNORs is significantly decreased. The AgNORs may serve as a marker for judgment of clinical treatment and supervisor.