Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer

BACKGROUND: Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen. PATIENTS AND METHODS: Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m(2), with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m(2)) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day). RESULTS: Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days. CONCLUSION: Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed

Interaction of photons with plasmas and liquid metals: photoabsorption and scattering

Formulas to describe the photoabsorption and the photon scattering by a plasma or a liquid metal are derived in a unified manner with each other. It is shown how the nuclear motion, the free-electron motion and the core-electron behaviour in each ion in the system determine the structure of photoabsorption and scattering in an electron-ion mixture. The absorption cross section in the dipole approximation consists of three terms which represent the absorption caused by the nuclear motion, the absorption owing to the free-electron motion producing optical conductivity or inverse Bremsstrahlung, and the absorption ascribed to the core-electron behaviour in each ion with the Doppler correction. Also, the photon scattering formula provides an analysis method for experiments observing the ion-ion dynamical structure factor (DSF), the electron-electron DSF giving plasma oscillations, and the core-electron DSF yielding the X-ray Raman (Compton) scattering with a clear definition of the background scattering for each experiment, in a unified manner. A formula for anomalous X-ray scattering is also derived for a liquid metal. At the same time, Thomson scattering in plasma physics is discussed from this general point of view.Comment: LaTeX file: 18 pages without figur

Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer

Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006–2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20⁺ B cells, CD8⁺ T cells, CD4⁺ T cells, and CD38⁺ plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044–0.536; P = 0.003). Patients with TLSs that included CD23⁺ germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20⁺ B cells was significantly larger in patients with TLSs than in those without TLS (P < 0.001). CD20⁺ B cells numbers were positively correlated with other TLSs. The larger number of CD20⁺ B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer

Development of a novel artificial intelligence algorithm to detect pulmonary nodules on chest radiography

Background: In this study, we aimed to develop a novel artificial intelligence (AI) algorithm to support pulmonary nodule detection, which will enable physicians to efficiently interpret chest radiographs for lung cancer diagnosis. Methods: We analyzed chest X-ray images obtained from a health examination center in Fukushima and the National Institutes of Health (NIH) Chest X-ray 14 dataset. We categorized these data into two types: type A included both Fukushima and NIH datasets, and type B included only the Fukushima dataset. We also demonstrated pulmonary nodules in the form of a heatmap display on each chest radiograph and calculated the positive probability score as an index value. Results: Our novel AI algorithms had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.74, a sensitivity of 0.75, and a specificity of 0.60 for the type A dataset. For the type B dataset, the respective values were 0.79, 0.72, and 0.74. The algorithms in both the type A and B datasets were superior to the accuracy of radiologists and similar to previous studies. Conclusions: The proprietary AI algorithms had a similar accuracy for interpreting chest radiographs when compared with previous studies and radiologists. Especially, we could train a high quality AI algorithm, even with our small type B data set. However, further studies are needed to improve and further validate the accuracy of our AI algorithm

CXCL13-producing CD4⁺ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer

卵巣がんにおける新たな免疫の仕組みを発見 --三次リンパ様構造の形成メカニズムと予後への影響を解明--. 京都大学プレスリリース. 2022-08-05.Tertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood. We investigated TLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression in high grade serous ovarian cancer (HGSC) specimens. CXCL13 gene expression correlated with TLS presence and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. Coexistence of CD8⁺ T cells and B-cell lineages in the TME significantly improved the prognosis of HGSC and was correlated with the presence of TLSs. CXCL13 expression was predominantly coincident with CD4⁺ T cells in TLSs and CD8⁺ T cells in TILs, and shifted from CD4⁺ T cells to CD21⁺ follicular dendritic cells as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8⁺ T cells. These results suggest that TLS formation was associated with CXCL13-producing CD4⁺ T cells and that TLSs facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer