Radiation therapy (RT) is an effective treatment modality for hepatocellular carcinoma (HCC), but globally, it is underutilized. In Russia, practice patterns with regard to liver-directed radiation ...are unknown. Under the auspices of Russian Society of Clinical Oncology (RUSSCO), our team conducted an IRB-approved contouring workshop for Russian radiation oncologists. Pre- and post-workshop surveys were analyzed to determine baseline clinical experience and patterns of care for liver-directed RT among Russian providers. The effect of the contouring workshop on participants’ knowledge was tested using mixed effects model. Forty pre-workshop and 24 post-workshop questionnaires were analyzable with a 100% response rate. Sixty percent of respondents had never evaluated a patient with HCC and only 8% (3 out of 40) reported treating an HCC patient with liver-directed RT. Nonetheless, 73% of respondents were comfortable offering liver-directed RT prior to the workshop. After the workshop, 85% of respondents felt comfortable treating a patient with HCC with liver-directed RT and 50% were comfortable recommending stereotactic body radiation therapy (SBRT). Measures of knowledge pertaining to evaluation of HCC patients and selection for appropriate liver-directed therapies were dramatically improved after the workshop. Liver-directed RT is not commonly used in Russia in the management of patients with HCC, and few centers are equipped for motion management. Our contouring workshop resulted in dramatically improved understanding of the evaluation and management of HCC patients. We recommend starting with a more protracted fractionated RT and building experience through attendance of additional educational activities, participation in multidisciplinary liver tumor boards, and prospective analysis of treatment toxicity and outcomes.
Highlights • Two ALK testing (FISH and IHC + FISH) algorithms were used for screening. • IHC + FISH for equivocal/positive cases demonstrated the best reliability. • Investigation of discrepant ...IHC/FISH cases clarified ALK status in all cases. • Additional investigations of these cases must be included in the testing algorithm.
Background
Real‐world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous.
Aim
RENSUR3 registry study assessed real‐world data on ...the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus.
Methods
Patients were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were patient characteristics, treatment patterns, and OS.
Results
1094 mRCC patients were identified. Mean age was 62.3 (SD, 11.2) years. Four hundred and forty‐four (41%) patients were 65 years and older. Primary tumor has not been removed in 503 (46%) patients. Subtype of RCC based on WHO classification (clear‐cell or other) has been reported in 402 (37%) patients. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients (≥65) were not treated compared to 37% of younger patients. Cytokines and targeted therapy were used in 298 (50.1%) and 297 (49.9%) of 595 treated patients, respectively. Median OS was 11.9 months (95% CI 10.9‐12.9). The 1‐ and 3‐year OS rates were 49.6% and 19.3%.
Conclusions
Half of patients received no systemic therapy or had only cytokines for mRCC in Russia, Kazakhstan, and Belarus, which doubtless negatively affected OS in this population. Novel therapies should be considered as life prolonging and a priority.
This study was aimed to evaluate distribution of epidermal growth factor receptor (EGFR) mutations in a large series of Russian lung cancer (LC) patients.
10,607 LC samples were considered for EGFR ...analysis; EGFR status was successfully determined in 10,426 cases (98.3 %), indicating relatively low failure rate.
EGFR mutations (ex19del and L858R) were detected in 1759/8716 (20.2 %) adenocarcinomas, 28/669 (4.2 %) squamous cell carcinomas (SCC) and 8/119 (6.7 %) large cell carcinomas. The occurrence of EGFR mutations in adenocarcinomas gradually increased with age, being attributed mainly to the increment of the L858R frequency in non-smokers (patients aged 18-30 years: 1/27 (3.7 %); 31-40 years: 5/98 (5.1 %); 41-50 years: 18/276 (6.5 %); 51-60 years: 102/944 (10.8 %); 61-70 years: 138/1011 (13.7 %); 71-80 years: 85/496 (17.1 %); 81-100 years: 5/27 (18.5 %); p < 0.0001). The EGFR mutation was detected in 804/2107 (38.2 %) non-smoking women versus 125/806 (15.5 %) non-smoking men (p < 0.0001), while the corresponding figures for smokers were 60/273 (22.0 %) versus 147/2214 (6.6 %) (p < 0.0001). The obtained gender-related data differ from the estimates obtained in Asian studies; they indicate that increased prevalence of EGFR mutations in white females may not be entirely attributed to the low prevalence of smoking, but is likely to be related to gender factors per se.
Biological causes of distinct age- and gender-related distribution of EGFR mutations in LC deserve further investigation.
There is the evidence of the role of the fibroblast growth factor and its receptors (FGF/FGFR) signaling pathway in tumorogenesis of renal cell carcinoma (RCC). We conducted a study aimed at ...evaluating of FGF2, FGFR1, and FGFR2 expression in primary tumor cells and assessing of these molecules expression levels effect on the characteristics of the tumor process and prognosis of patients with RCC.
Expression of FGF2, FGFR1, and FGFR2 was investigated in 65 primary RCC specimens by immuhistochemical staining using the appropriate antibodies. Expression levels were evaluated by the semi-quantitative method. A search for correlations of expression levels of investigated growth factors and receptors with RCC features and patients outcomes was performed.
Cytoplasm and membrane expression of FGF2, FGFR1, and FGFR2 was found in the primary tumor cells of RCC patients. FGF2 staining was detected in 60.0% of cases (44.2 ± 5.4 HS). It was noted higher frequency and intensity of FGFR2 expression (66.2%; 46.6 ± 6.3 HS) comparing with FGFR1 (32.3%; 7.5 ± 2.2 HS). The correlation was revealed between the investigated markers overexpression and Fuhrman grade G3-4, as well as features of advanced RCC (paranephric fat tumor invasion, venous wall tumor invasion, adrenal and liver metastases). FGFR2 overexpression showed negative influence on cancer-specific survival in univariate analysis, however, lost its predictive value in multivariable analysis.
Expression of FGF2 and its receptors was found on the surface and in the cytoplasm of RCC primary tumor cells and needs following investigations.
Background: Introduction of immune checkpoint inhibitors in the standard of care for metastatic renal cell carcinoma (mRCC) requires robust but yet simple biomarkers to predict efficacy of ...immunotherapy. Objective: The aim of this study was to evaluate the association between fibrinogen levels and efficacy of second-line therapy with nivolumab in mRCC. Methods: This is a prospective multicenter biomarker study. Fibrinogen levels were measured one week prior to second-line nivolumab therapy and six times monthly. A high fibrinogen level was defined as ≥5 g/L. Patients were divided into two cohorts: high (H) and normal (N) fibrinogen levels. The primary endpoint was overall survival (OS). Results: The median OS was 31.5 months (95% confidence interval CI, 27.9 to 35.1) in cohort N vs. 20.9 months (95% CI, 18.1 to 23.7) in cohort H (hazard ratio HR, 0.39; 98.5% CI, 0.21 to 0.7; P = 0.002). The median progression-free survival was 9.4 months (95% CI, 5.5 to 14.1) in cohort N and 4.0 months (95% CI, 2.9 to 5.1) in cohort H (HR, 0.65; 95% CI, 0.51 to 0.72; P < 0.001). The objective response rate was higher in N cohort (33% vs. 17% ; P = 0.012). No statistically significant changes of fibrinogen concentration during nivolumab therapy were found. Conclusion: The study demonstrated an association of hyperfibrinogenemia with worse clinical outcomes of second-line nivolumab monotherapy in patients with mRCC. Further validation of fibrinogen as a predictive biomarker for immunotherapy efficacy in patients with mRCC is warranted.
Background
Definitive concurrent chemoradiation (cCRT) is offered to only 3% of Russian patients with stage III NSCLC. To determine the patterns of care and barriers to cCRT utilization in Russia, we ...conducted a survey of practicing radiation oncologists (ROs).
Methods
Electronic IRB-approved survey containing 15 questions was distributed to Russian ROs. Fisher’s exact test or Cochran-Armitage test of trend was used to assess the associations between clinical experience, practice type, and patterns of care.
Results
We analyzed 58 questionnaires completed by ROs—16 respondents from tertiary referral hospitals, and 42 from community or private centers. A total of 88% of respondents formulate treatment recommendations in multi-disciplinary tumor boards. For unresectable stage III NSCLC, the most common recommendation is sequential CRT (50%), followed by concurrent CRT (40%), with an observed higher utilization of cCRT in tertiary centers (9/16, 56% vs 14/42, 33%). Of the respondents, 31% do not offer cCRT to their pts. Among reasons for avoiding cCRT are (1) poor performance of pts (76%); (2) high toxicity of therapy (55%); (3) lack of consensus among tumor board members (33%); and (4) preference for sequential CRT (31%). Only 3% do not irradiate elective LNs. Eighty-six percent of respondents counsel their NSCLC pts regarding smoking cessation.
Conclusions
Despite level 1 evidence, cCRT is rarely used in Russia for pts with locally advanced NSCLC, and preference for sequential therapy and concerns over high toxicity are the most common barriers. Education of Russian ROs may increase cCRT utilization, leading to improved survival, notably in the era of maintenance immunotherapy.
RENSUR5 is a large ‘real-world’ database assessing metastatic renal cell carcinoma (mRCC) treatment patterns and 5-year overall survival (OS) in Russia. Five-year OS was 8.2%. Based on results of ...this study, we assume that 5-year OS should be improved on novel therapies.
The 5-year overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC) has been rarely reported. The aim of the RENSUR5 registry study was to obtain real-world data on the use of therapy for mRCC and assess the 5-year OS in the Russian population.
Patients were retrospectively identified at 11 cancer centers in different regions of Russia (Astrakhan, Barnaul, Ekaterinburg, Kazan, Krasnoyarsk, Obninsk, Omsk, Rostov-on-Don, Samara, St. Petersburg, and Ufa). Patients were included if mRCC had been diagnosed from January 2010 to January 2011. Anonymized data were collected through an online registry covering the demographic data, treatments, and outcomes.
A total of 439 adult mRCC patients were included in the present study for analysis. The mean age at diagnosis of mRCC was 60.9 years (range, 33-90 years; with 9% of patients aged ≥ 75 years). The patients were predominantly men (70.2%) and 67.7% had nephrectomy. Clear cell and non–clear cell tumors were detected in 61.1% and 7.7% of patients, respectively. A total of 271 patients (62%) received systemic therapy. The median duration of therapy was 11 months (95% confidence interval, 9.5-12.5 months). Most treatment was with interferon only (n = 145); 105 patients (23.9%) received targeted therapy, and 69 patients (15.7%) received ≥ 2 treatment lines. The 1-, 3-, and 5-year OS rate was 49.4%, 18.9%, and 8.2%, respectively. The median OS from the start of treatment was 12 months (95% confidence interval, 9.7-14.4 months).
RENSUR5 is a large real-world database assessing the mRCC treatment patterns and 5-year OS in Russia. According to the first results of the present study, we believe that 5-year OS should improve with novel therapies. The limited administration of targeted therapies was reflected by the results of the 5-year survival rate. The treatment of mRCC has changed in the past years with new treatment options significantly improving OS. The 5-year OS of patients treated with immunotherapy and targeted therapy should be analyzed in the real world.
Material and methods Expression of vascular endothelial growth factor (VEGF)A, fibroblast growth factor (FGF)2, vascular endothelial growth factor receptor (VEGFR)l, VEGFR2, FGFR1, FGFR2, ...platelet-derived growth factor receptor (PDGFR)a, and PDGFR(3 was investigated in 65 primary RCC specimens by immuhis-tochemical staining using the appropriate antibodies. KeyWords: renal cell carcinoma primary tumor vascular endothelial growth factor fibroblast growth factor platelet-derived growth factor INTRODUCTION Mitogenesis, angiogenesis, and lymphangiogenesis underlying renal cell carcinoma (RCC) progression are associated with a high level of hypoxia-induced factor (HIF) and growth factors in the tumor micro-environment. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and their receptors such as VEGFR, FGFR and platelet-derived growth factor receptors (PDGFR) are considered to be involved in this dynamic process 1-4. The trial was approved by the N.N. Blokhin Russian Cancer Research Center review board, and complied with the Good Clinical Practice guidelines, the Declaration of Helsinki, and local laws.
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