Yuki Sato

Energy resolution of gas ionization chamber for high-energy heavy ions

The energy resolution is reported for high-energy heavy ions with energies of nearly 340 MeV/nucleon and was measured using a gas ionization chamber filled with a 90%Ar/10%CH4 gas mixture. We observed that the energy resolution is proportional to the inverse of the atomic number of incident ions and to the inverse-square-root of the gas thickness. These results are consistent with the Bethe–Bloch formula for the energy loss of charged particles and the Bohr expression for heavy ion energy straggling. In addition, the influence of high-energy δ-rays generated in the detector on the energy deposition is discussed.

Kinetic-energy-sensitive mass spectrometry for separation of different ions with the same m/z value

A double-focusing mass spectrometer (MS) equipped with a superconducting-tunnel-junction (STJ) detector has been applied to measure relative ionization cross-sections for the production of ions that are accompanied by different ion species with the same mass-to-charge (m/z) value. The STJ detector fabricated for this study enables kinetic energy (E) measurement of incoming individual ions at a counting rate of up to approximately 100 k ions/s and an energy resolution (DeltaE/E) of 15%. Both high counting rate and high-energy resolution are necessary to independently determine both m and z and not the m/z value only in ion-counting MS experiments. Ions such as (14)N(2) (2+) and (14)N(+) with the same m/z value can be clearly discriminated using a kinetic-energy-sensitive MS. This fine discrimination capability allows direct determination of relative ionization cross-sections of the homonuclear diatomic ions (14)N(2) (2+)/(14)N(2) (+) and (16)O(2) (2+)/(16)O(2) (+), which are difficult to measure due to the strong interference by the signals of their dissociated atomic ions with noticeably large ionization cross-sections. The new instrument requires no low-abundance heteronuclear diatomic molecules of the forms (14)N(15)N or (16)O(17)O to carry out ionization studies and thus, is expected to be useful in fields such as atmospheric science, interstellar science, or plasma physics.

Enteral Nutrition Is a Risk Factor for Airway Complications in Subjects Undergoing Noninvasive Ventilation for Acute Respiratory Failure

BACKGROUND: Early enteral nutrition is recommended for mechanically ventilated patients in several studies and guidelines. In contrast, the effects of early enteral nutrition on noninvasive ventilation (NIV) have not been investigated extensively. The lack of an established method of airway protection suggests that enteral nutrition administration to these patients could increase airway complications and worsen outcomes. METHODS: Between January 2007 and January 2015, 150 patients were admitted to our respiratory department for acute respiratory failure and received NIV for >48 h. Of these, 107 subjects incapable of oral intake were retrospectively analyzed. Clinical background and complications were compared in subjects who did and did not receive enteral nutrition. RESULTS: Sixty of the 107 subjects (56%) incapable of oral intake who received NIV also received enteral nutrition. Serum albumin concentration was significantly lower in subjects who received enteral nutrition than in those who did not (mean 2.7 ± 0.68 mg/dL vs 3.0 ± 0.75 mg/dL, P = .048). The rate of airway complications was significantly higher (53% [32/60] vs 32% [15/47], P = .03), and median NIV duration was significantly longer (16 [interquartile range 7–43] d vs 8 [5–20] d, P = .02) in subjects who received enteral nutrition than in those who did not. Multivariate analysis showed that enteral nutrition was unrelated to in-hospital mortality. CONCLUSIONS: Among subjects receiving NIV, enteral nutrition was associated with increased risk of airway complications but did not affect mortality. Enteral nutrition should be carefully considered in these patients.

Early Immune-Related Adverse Events and Association with Outcome in Advanced Non–Small Cell Lung Cancer Patients Treated with Nivolumab: A Prospective Cohort Study

Introduction Retrospective studies have shown immune‐related adverse events (irAEs) to be associated with better prognosis. However, no prospective clinical trials have been conducted, and little is known regarding the association between irAEs and the outcome of patients with NSCLC after treatment with immunotherapy. Methods We conducted a prospective cohort study of patients with advanced NSCLC who were treated with nivolumab between January and December 2016. The association between clinical outcome and irAEs 2 to 6 weeks after commencement of nivolumab treatment was investigated. IrAEs were assessed by at least three independent medical professionals. Results A total of 43 patients were enrolled, including 19 patients with irAEs 2 weeks after commencement of nivolumab treatment. Common irAEs included rash, pyrexia, and diarrhea. Programmed cell death ligand 1‐positive tumor cell expression was not significantly different between patients with and without irAEs. The objective response and disease control rates were higher in patients with irAEs than in those without irAEs (37% versus 17% and 74% versus 29% [p = 0.17 and p < 0.01], respectively]). Patients with irAEs were associated with a significantly longer median progression‐free survival than those without (6.4 months [95% confidence interval: 2.5‐not reached] versus 1.5 months [95% confidence interval: 1.2–2.3] [p = 0.01]). These findings were comparable to those for patients with and without irAEs 6 weeks after commencement of nivolumab treatment. Conclusions Early irAEs are associated with a better outcome after treatment with immunotherapy. We predicted responses to nivolumab by using early irAEs. Further research is needed to elucidate the mechanisms of these associations.

Pulse height reduction effects of single-crystal CVD diamond detector for low-energy heavy ions

The performance of a diamond detector made of single-crystal diamond grown by chemical vapour deposition was studied for heavy ions, having energy of 3 MeV. Energy peaks of these low-energy ions were clearly observed. However, the pulse height for individual incident ion decreases with increasing atomic number of the ions. For understanding this pulse height reduction effect, we calculated the amount of ionizing and non-ionizing energy loss of incident ions in the diamond detector. The results of our calculation suggest the contribution of charge loss mechanisms other than the recombination effect of electron-hole pairs produced along the ionized track. We also mentioned the incomplete charge collection near the boundary region between the metal electrode and the diamond surface.

Single-crystal CVD diamond detector for high-resolution particle spectrometry

The performance of a single-crystal diamond detector, grown by chemical vapour deposition, as an energy spectrometer for charged particles was studied. The detector was able to identify four different energies of -particles (5.389, 5.443, 5.486, and 5.545 MeV) thanks to a superior intrinsic energy resolution of (full width at half maximum). The electrode configuration, specifically the electric field configuration inside the diamond crystal, and the electrode materials, strongly affect the energy resolution for charged particles. The charge collection efficiency inside the diamond crystal was for both electrons and holes.

Pulse height reduction effects of superconducting tunnel junction particle detectors for low-energy light molecular ions

The performance of particle detectors using superconducting tunnel junctions has been studied for metal cluster or molecular ions accelerated at 3keV. The output pulse height for individual ion impact decreases as the mass of projectiles increases in a mass range of less than 800amu. In addition, pulse height reduction effects strongly depend on the molecular species. These phenomena are understood by taking into account secondary electron emission that carries part of the deposited kinetic energies of ion away from the junction surface.

A pilot trial of nivolumab treatment for advanced non-small cell lung cancer patients with mild idiopathic interstitial pneumonia

INTRODUCTIONnNivolumab has demonstrated efficacy against metastatic non-small cell lung cancer (NSCLC). However, immune-related adverse events can occur, among which pneumonitis is relatively common. Lung cancer patients with idiopathic interstitial pneumonia (IIP) have a higher risk of pneumonitis associated with anticancer therapy. We hypothesized that the benefit of nivolumab may outweigh the risks of pneumonitis in patients with NSCLC who have mild IIP. We performed a pilot trial to evaluate the safety of nivolumab in NSCLC patients with mild IIP.nnnMETHODSnPreviously treated, inoperable NSCLC patients with mild IIP were enrolled. Mild IIP was defined as having a predicted vital capacity ≥80% and a possible usual interstitial pneumonia (UIP) or inconsistent with UIP pattern on chest high-resolution computed tomography. Patients received nivolumab at a dose of 3mg/kg biweekly.nnnRESULTSnSix patients were enrolled in this trial between April 2016 and December 2016. None experienced drug-related nonhematologic grade 3/4 or hematologic grade 4 adverse events in the 12 weeks following the initiation of nivolumab treatment. Furthermore, none of the patients had pneumonitis of any grade. At the time of analysis, all patients were alive, and 3 had experienced a partial response.nnnCONCLUSIONSnNivolumab therapy may be feasible in NSCLC patients with mild IIP. (Trial registration number: UMIN000022037).

Alteration of PD-L1 expression and its prognostic impact after concurrent chemoradiation therapy in non-small cell lung cancer patients

Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (Pu2009=u20090.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (Pu2009<u20090.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.

Predictive Performance of Four Programmed Cell Death Ligand 1 Assay Systems on Nivolumab Response in Previously Treated Patients with Non–Small Cell Lung Cancer

Introduction: Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD‐L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy. Methods: We retrospectively analyzed patients with previously treated advanced NSCLC, who received nivolumab between January 2016 and September 2016. Specimens were stained using four PD‐L1 IHC assays (28‐8, 22C3, SP142, and SP263). We classified patients as having test results that were strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS 1%–49%), or negative (TPS <1%). Results: A total of 40 patients with NSCLC and their specimens were analyzed. Analytical comparisons demonstrated good concordance of PD‐L1–stained tumor cells among the 28‐8, 22C3, and SP263 assays (weighted &kgr; coefficient 0.64–0.71), whereas the SP142 assay showed lower concordance with other assays (weighted &kgr; coefficient 0.39–0.55). Progression‐free survival in patients showing strongly positive PD‐L1 staining classified by 28‐8, 22C3, and SP263 assays was significantly longer than that in patients with a negative result for PD‐L1 staining. Predictive performance of response to nivolumab, as assessed by receiver operating characteristic analysis, was also equivalent among the 28‐8, 22C3, and SP263 assays (area under the curve 0.75–0.82), whereas the SP142 assay exhibited lower predictive performance (area under the curve 0.68). Conclusions: The 28‐8, 22C3, and SP263 PD‐L1 IHC assays showed equivalent predictive performance, whereas the SP142 assay showed lower predictive performance.