Search

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Hiroki Kobayashi,1 Yamato Wada,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the eosinophil changes, efficacy and safety of pembrolizumab treatment in advanced urothelial carcinoma patients of older age and those with a poor performance status (PS).Materials and Methods: Consecutive patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy between January 2018 and June 2021 were retrospectively examined.Results: 105 patients (median age, 72 years), 71.4% of whom were men, were enrolled. Patients of ≥ 75 years of age were considered to be older patients (n=40), and patients with PS ≥ 2 were considered to have a poor PS (n=10). The objective response and disease control rates were 42.5% and 52.5%, respectively, in older patients and 0% and 10.0%, respectively, in patients with a poor PS. Overall survival (OS) in the older and younger groups did not differ to a statistically significant extent. However, a poor PS was significantly associated with poor survival. Safety analyses demonstrated no significant difference in the occurrence of any immune-related adverse events (irAEs), including grade ≥ 3, between the older and younger groups. However, a poor PS was significantly associated with the low occurrence of any irAEs. The change of the eosinophil count, the increase of the relative eosinophil count (REC) and the decrease of the neutrophil-to-eosinophil ratio (NER) did not differ to a statistically significant extent between the older and younger groups, but showed significant differences between the poor and good PS (PS 0– 1) groups.Conclusion: Pembrolizumab for advanced UC demonstrated similar changes in the eosinophil count, efficacy and toxicity in both older and younger patients. In patients with a poor PS, although toxicity was significantly lower, survival was significantly worse, and neither an increase in REC nor a decrease in NER were observed, but these values showed significant changes in patients with a good PS.Keywords: urothelial carcinoma, pembrolizumab, age, performance status, immune-related adverse events, relative eosinophil count, neutrophil-to-eosinophil ratio

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Akihiro Miura,1 Hiroki Komori,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined.Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P< 0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥ 3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥ 3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥ 1 (P=0.024), albumin < 3.7 g/dl (P< 0.001), decreased REC (3 weeks later) (P< 0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS.Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.Keywords: urothelial carcinoma, pembrolizumab, immune-related adverse events, relative eosinophil count

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Shingo Tamura,7 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab.Materials and Methods: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk.Results: There were no significant differences in the overall survival (OS) between the REC ≥ 4.8% and < 4.8% groups and the NER ≥ 13.7 and < 13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p< 0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥ 2 (P=0.003), albumin < 3.7 g/dl (p=0.002), LDH > 246 U/L (p=0.011), disease site ≥ 3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS.Conclusion: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.Keywords: urothelial carcinoma, pembrolizumab, eosinophil, neutrophil-to-eosinophil ratio

Nobuki Furubayashi,1 Takahito Negishi,1 Naotaka Sakamoto,2 Hozumi Shimokawa,3 Futoshi Morokuma,4 Yoohyun Song,5 Yoshifumi Hori,6 Toshihisa Tomoda,7 Noriaki Tokuda,4 Narihito Seki,5 Kentaro Kuroiwa,6 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 3Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Saga-ken Medical Centre Koseikan, Saga, Japan; 5Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 6Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 7Department of Urology, Oita Prefectural Hospital, Oita, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-Ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC).Materials and Methods: Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1.Results: We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9‑13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p< 0.001).Conclusion: Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.Keywords: urothelial carcinoma, platinum-based chemotherapy, pembrolizumab, organ-specific response rate, tumor microenvironment

Three composites composed of the cobalt terpyridine complex [CoII(MeO-terpy)2] and the diblock copolypeptide amphiphiles 1 and 2 or the polypeptide 3 (including glutamic acid and leucine) were prepared. Supramolecular structures such as rectangular morphologies were obtained from composites of 1 and 2. A perfectly reversible reverse spin transition was successfully generated in the case of composites made with 1.

Two of the most intensively studied processes in the field of ecological physiology are the limits to metabolic performance and the energetics of temperature acclimation. A major emphasis currently is the examination of relationships among basal metabolic rate (BMR), maximum metabolic rate (MMR), and the sizes of vital organs and tissues such as kidneys, liver, heart, and skeletal muscle. We examined these relationships in house finches (Carpodacus mexicanus) that were maintained in the laboratory at two different acclimation temperatures. Birds in the cold-acclimation (CA) group were maintained at [5.sup.f] C, and those in the warm-acclimation (WA) control group at [25.sup.f] C, for six weeks following capture in New York in June. All metabolic rate values were measured as oxygen consumption in an open-circuit respirometry system. MMR was determined by two methods for each animal: exercise maximum in a running wheel chamber and thermogenic maximum during exposure to cold temperatures in a helium-oxygen (heliox) atmosphere. The body mass of CA birds (20.1 [+ or -] 0.5 g) was significantly greater (p [is less than] 0.001) than that of WA birds (18.4 [+ or -] 0.3 g). Even when adjusted for differences in body mass, the BMR of CA birds was 15% greater than that of WA individuals (p [is less than] 0.01). However, there was no effect of acclimation temperature on either exercise or cold-induced MMR. Exercise-induced MMR values were 17.5% greater than those obtained using the heliox protocol (p [is less than] 0.01). The relationships among organ sizes and metabolic measurements will be discussed.