Recent trends in bone metastasis treatments:A historical comparison using the new Katagiri score system

BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.

High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.

Influence of FeO and sulfur on solid state reaction between MnO-SiO_2-FeO oxides and an Fe-Mn-Si solid alloy during heat treatment at 1473 K

To clarify the influence of Fe O and sulfur on solid state reaction between an Fe-Mn-Si alloy and Mn O-Si O2-Fe O oxides under the restricted oxygen diffusion flux, two diffusion couples with different sulfur contents in the oxides were produced and investigated after heat treatment at 1473 K. The experimental results were also compared with previous work in which the oxides contained higher Fe O. It was found that although the Fe O content in the oxides decreased from 3wt% to 1wt% which was lower than the content corresponding to the equilibrium with molten steel at 1873 K, excess oxygen still diffused from the oxides to solid steel during heat treatment at 1473 K and formed oxide particles. In addition, increasing the sulfur content in the oxides was observed to suppress the diffusion of oxygen between the alloy and the oxides.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUND Angiogenesis inhibitors(AIs)combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer(CRC).Aflibercept(AFL)is an option for second-line treatment of CRC,according to the‘VELOUR’trial.Currently,we can choose from three AIs,including bevacizumab,ramucirumab,and AFL.Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action.We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIM To determine and compare the efficacy and safety profiles of AFL in the secondline and salvage therapy settings.METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan(FOLFIRI)regimen were collected retrospectively from six institutions in Japan,for the period from May 2017 to March 2019.Patient characteristics collected included age,sex,tumor location,RAS and RAF status,metastatic sites,number of previous treatment cycles,therapeutic response,adverse events,duration of previous AI treatment,and survival time.The end points were time to AFL treatment failure(aTTF)and median survival time post-AFL(aMST).Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting,which was defined as the days since the end of secondline therapy.RESULTS All 41 patients who received AFL+FOLFIRI for advanced CRC had metastatic or unresectable cancer.Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting.The patient characteristics were similar in the two groups,except for two factors.The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients(144 d vs 323 d,P=0.006).In the second-line and salvage therapy groups,the objective response rates were 11%and 0%,respectively(P=0.50),and the disease control rates were 53%and 50%,respectively(P=1.00).In the second-line and salvage therapy groups,the aTTF(123 d vs 71 d,respectively),aMST(673 d vs 396 d,respectively),and incidence of adverse events of grade 3[8(36%)vs 9(47%)]were not significantly different between the two groups.CONCLUSION AFL can be used to treat advanced CRC patients,with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Numerical and Experimental Investigation on Heat Propagation Through Composite Sinter Bed With Non-Uniform Voidage:Part Ⅰ Mathematical Model and Its Experimental Verification

The mechanisms of heat transfer through the sinter beds of the MEBIOS process are discussed and their comprehensive mathematical model is proposed. The MEBIOS process, the concept of which has been proposed ear- lier by the authors, allows using both coarse and fine particles of iron ores in the same sinter bed. The study includes two parts. The first part describes the model content and the results of its experimental verification. The model ac- counts for coal combustion, limestone decomposition, moisture evaporation/condensation, and melting/solidifying of solid phases. The model predictions are in good agreement with the experimental data. Typical numerical results of the sintering process and the key parameters influencing the process efficiency are discussed in the second part of the study.

Numerical and Experimental Investigation on Heat PropagationThrough Composite Sinter Bed With Non-Uniform Voidage:Part Ⅱ Prediction of Process Efficiency

The results of numerical simulation of the mosaic embedding iron ore sintering （MEBIOS） process according to the model presented in the first part of the study are introduced. The main objective of the second part is the elucidation of key factors influencing the process efficiency, particularly the sintering completeness, velocity of the heat wave propagation and maximum temperature achievable in the pellet during the wave propagation. Numerical results reveal that the mass fraction of coal, diameter of coal particles and air inlet velocity are of prime importance in determining efficiency of the MEBIOS sintering process.