In patients with renal cell carcinoma, brain metastasis is generally one of the poor prognostic factors. However, the recent introduction of molecular target therapy and immune checkpoint inhibitor ...has remarkably advanced the systemic treatment of metastatic renal cell carcinoma and prolonged the patients’ survival. The pivotal clinical trials of those agents usually excluded patients with brain metastasis. The incidence of brain metastasis has been increasing in the actual clinical setting because of longer control of extra-cranial disease. Brain metastasis subgroup data from the prospective and retrospective series have been gradually accumulated about the risk classification of brain metastasis and the efficacy and safety of those new agents for brain metastasis. While the local treatment against brain metastasis includes neurosurgery, stereotactic radiosurgery, and conventional whole brain radiation therapy, the technology of stereotactic radiosurgery has been especially advanced, and the combination with systemic therapy such as molecular target therapy and immune checkpoint inhibitor is considered promising. This review summarizes recent progression of multimodality treatment of brain metastasis of renal cell carcinoma from literature data and explores the future direction of the treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The 150 year history of the Japanese steel industry dates from the first western blast furnace, which was built by T. Ohashi in 1857. Modern blast furnace operation at integrated steel works in Japan ...started in 1901 with the first blow-in of Higashida No. 1 blast furnace at Yawata Steel Works. Throughout the prewar and postwar periods, the steel industry has supported the Japanese economy as a key industry which supplies basic materials for social infrastructure and development. After the period of recovery following the destruction caused by World War II, Chiba Works of Kawasaki Steel Corporation (now JFE Steel Corporation) was built and began operation in 1953 as the first integrated steel works in the Keiyo Industrial Region after the war. During Japan’s period of high economic growth, many coastal steel works with large blast furnaces having inner volumes of more than 3000 m3 and even 5000 m3 were built to enable efficient marine transportation of raw materials and steel products. Japanese steel makers introduced and improved the most advanced technologies of the day, which included high pressure equipment, stave cooler systems, bell-less charging systems, etc. As a result, Japanese steel works now lead the world in low reducing agent rate (RAR) operation, energy saving, and long service life of blast furnaces and coke ovens. Following the Oil Crises of the 1970s, the Japanese steel industry changed energy sources from oil to coal and implemented cost-oriented operation design and technology. In 2012, the Japanese steel industry produced approximately 80 million tons of hot metal from 27 blast furnaces, including large-scale furnaces with inner volumes over 5000 m3. During this period, the industry has faced many economic and social challenges, such as the high exchange rate of the yen, oligopoly in the mining industry, global warming, and the surge in iron ore and coal prices driven by the rapid growth of the BRICs. The industry has successfully responded to these challenges and maintained its international competitiveness by developing advanced technologies for pulverized coal injection, expanded use of low cost iron resources, recycling for environmental preservation, and CO2 mitigation. In this paper, the prospects for ironmaking technologies in the coming decades are described by reviewing published papers and looking back on the history of developments in ironmaking during the last 100 years.
Previous clinical trials indicate that 10%–25% of patients received genomically matched therapy after comprehensive genomic profiling (CGP) tests. However, the clinical utility of CGP tests has not ...been assessed in clinical practice. We assessed the clinical utility of CGP tests for advanced or metastatic solid tumor and determined the proportion of patients receiving genomically matched therapy among those with common and non‐common cancers. From August 2019 to July 2020, a total of 418 patients had undergone CGP tests, and the results were discussed through the molecular tumor board at our site. The median age of patients was 57 (range: 3–86) years. Colorectal cancer was the most common, with 47 (11%) patients. Actionable genomic alterations (median 3, range: 1–17) were identified in 368 (88.0%) of 418 patients. Druggable genomic alterations were determined in 196 (46.9%) of 418 patients through the molecular tumor board. Genomically matched therapy was administered as the subsequent line of therapy in 51 (12.2%) patients, which is comparable to the proportion we previously reported in a clinical trial (13.4%) (p = 0.6919). The proportion of patients receiving genomically matched therapy was significantly higher among those with common cancers (16.2%) than non‐common cancers (9.4%) (p = 0.0365). Genomically matched therapy after the CGP tests was administered to 12.2% of patients, which is similar to the proportion reported in the previous clinical trials. The clinical utility of CGP tests in patients with common cancers greatly exceeded that in patients with non‐common cancers.
Genomically matched therapy after comprehensive genomic profiling (CGP) tests was administered to 12.2% of patients in clinical practice. We demonstrated the clinical utility of CGP tests in clinical practice, particularly among those with common cancers who received genomically matched therapy more frequently than those with non‐common cancers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with ...LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis‐free survival (MFS) was the primary outcome. Patients were stratified by prostate‐specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan‐Meier method and log‐rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15‐0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.
The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) among patients with persistent prostate‐specific antigen (PSA) after RP has not been established. Here, the outcomes of various management strategies among patients with LNI after RP were investigated. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to androgen deprivation therapy (ADT) might improve survival.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study ...collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil‐to‐lymphocyte ratio. The median OS times (95% confidence intervals CIs) for the low‐, intermediate‐, and high‐risk groups (discovery cohort) were not yet reached (NYR) (NYR–19.1), 6.8 mo (5.8‐8.9), and 2.3 mo (1.2‐2.6), respectively. The HRs (95% CI) for OS in the low‐ and intermediate‐risk groups vs the high‐risk group were 0.07 (0.04‐0.11) and 0.23 (0.15‐0.37), respectively. The objective response rates for in the low‐, intermediate‐, and high‐risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first‐line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab‐treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design.
A multicenter study using real‐world data of patients who received pembrolizumab treatment for chemoresistant urothelial cancer reports a prognostication model based on 4 risk factors (Eastern Cooperative Oncology Group performance status, site of metastasis, low hemoglobin, and high lymphocyte‐to‐neutrophil ratio). The model was developed using data from the first 463 patients and externally validated by an independent cohort of 292 patients with high concordance and reproducibility.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Management of bladder cancer in older patients Hatakeyama, Shingo; Narita, Shintaro; Okita, Kazutaka ...
Japanese journal of clinical oncology,
03/2022, Volume:
52, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract
Evidence has shown that patients with bladder cancer are diagnosed at a much older age compared with those with other cancers. Given that co-morbidities and frailty are prevalent in older ...patients with advanced bladder cancer, they are easily excluded from randomized controlled trials. As little evidence has been available regarding assessment tools for frailty, the management of those patients remains challenging. This weakness is strongly manifested in muscle-invasive bladder cancer. Despite radical cystectomy is the standard of care for bladder cancer, there is an extensive undertreatment of older adult patients with potentially curative muscle-invasive bladder cancer. However, it is also true that radical cystectomy is often unsuitable for vulnerable or frail patients. Bladder preservation using trimodality therapy has been utilized as an alternative option, but the appropriate selection criteria for trimodality therapy remain unclear. Cisplatin-based regimens have been the first choice for advanced disease among eligible patients. Moreover, immunotherapy appears to have similar benefits and tolerability in both older and younger patients. Furthermore, palliative or supportive interventions need to be initiated earlier in patients with metastatic disease. Accumulating evidence suggests that frailty may play a key role in the selection of treatment modalities. Older patients should be considered for standard treatment based on frailty and not chronological age. Moreover, older patients with bladder cancer need to undergo geriatric assessment for proper decision-making.
Management of locally advanced or metastatic bladder cancer in older patients is challenging. Standard treatment in older patients should be based on frailty and not on chronological age.
Management of prostate cancer in older patients Narita, Shintaro; Hatakeyama, Shingo; Sakamoto, Shinichi ...
Japanese journal of clinical oncology,
2022-May-31, Volume:
52, Issue:
6
Journal Article
Peer reviewed
Open access
Abstract
The incidence of prostate cancer among older men has increased in many countries, including Asian countries. However, older patients are ineligible for inclusion in large randomized trials, ...and the existing guidelines for the management of patients with prostate cancer do not provide specific treatment recommendations for older men. Therefore, generation of evidence for older patients with prostate cancer is a key imperative. The International Society of Geriatric Oncology has produced and updated several guidelines for management of prostate cancer in older men since 2010. Regarding localized prostate cancer, both surgery and radiotherapy are considered as feasible treatment options for intermediate- and high-risk prostate cancer even in older men, whereas watchful waiting and active surveillance are useful options for a proportion of these patients. With regard to advanced disease, androgen-receptor axis targets and taxane chemotherapy are standard treatment modalities, although dose modification and prevention of adverse events need to be considered. Management strategy for older patients with prostate cancer should take cognizance of not only the chronological age but also psychological and physical condition, socio-economic status and patient preferences. Geriatric assessment and patient-reported health-related quality of life are important tools for assessing health status of older patients with prostate cancer; however, there is a paucity of evidence of the impact of these tools on the clinical outcomes. Personalized management according to the patient’s health status and tumour characteristics as well as socio-economic condition may be necessary for treatment of older patients with prostate cancer.
This review focuses on the management of older patients with prostate cancer, particularly in Asian population, based on published literature and guidelines.
Through the support for reconstruction from the disaster of the great earthquake in the eastern Japan in 2011, The Iron Technology and History Forum” of the Iron and Steel Institute of Japan received ...a request to study the molten iron and steel production in low height furnace with iron-sand smelting, and started up “IMPRESSIVE”, the research workshop of the Iron Manufacturing Process Engineering and Scientific Study in Vetus Iron in 2013. The research workshop IMPRESSIVE has studied the process engineering of ironmaking with iron sand under dynamic states in a low height furnace. As results, in the iron-sand refining using a low-height furnace, the subjects of unit operations in the dynamic state are considered to be three couplings of reactivity of wood charcoal, basicity of iron sand and furnace structure with tuyere. Combining these unit operations, the metal discharge shows a variety including flow out like a serpent and its composition being converted into higher purity molten pig iron.
Renal cell carcinoma (RCC) comprises several histological types characterised by different genomic and epigenomic aberrations; however, the molecular pathogenesis of each type still requires further ...exploration. We perform whole-genome sequencing of 128 Japanese RCC cases of different histology to elucidate the significant somatic alterations and mutagenesis processes. We also perform transcriptomic and epigenomic sequencing to identify distinguishing features, including assay for transposase-accessible chromatin sequencing (ATAC-seq) and methyl sequencing. Genomic analysis reveals that the mutational signature differs among the histological types, suggesting that different carcinogenic factors drive each histology. From the ATAC-seq results, master transcription factors are identified for each histology. Furthermore, clear cell RCC is classified into three epi-subtypes, one of which expresses highly immune checkpoint molecules with frequent loss of chromosome 14q. These genomic and epigenomic features may lead to the development of effective therapeutic strategies for RCC.
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