This paper documents the production and validation of retrieved rainfall data obtained from satellite-borne microwave radiometers by the Global Satellite Mapping of Precipitation (GSMaP) Project. ...Using various attributes of precipitation derived from Tropical Rainfall Measuring Mission (TRMM) satellite data, the GSMaP has implemented hydrometeor profiles derived from Precipitation Radar (PR), statistical rain/no-rain classification, and scattering algorithms using polarization-corrected temperatures (PCTs) at 85.5 and 37 GHz. Combined scattering-based surface rainfalls are computed depending on rainfall intensities. PCT85 is not used for stronger rainfalls, because strong depressions of PCT85 are related to tall precipitation-top heights. Therefore, for stronger rainfalls, PCT37 is used, with PCT85 used for weaker rainfalls. With the suspiciously strong rainfalls retrieved from PCT85 deleted, the combined rainfalls correspond well to the PR rain rates over land. The GSMaP algorithm for the TRMM Microwave Imager (TMI) is validated using the TRMM PR, ground radar Kwajalein (KWAJ) radar and COBRA, and Radar Automated Meteorological Data Acquisition System (AMeDAS) precipitation analysis (RA). Monthly surface rainfalls retrieved from six microwave radiometers (GSMaP_MWR) are compared with the gauge-based dataset. Rain rates retrieved from the TMI (GSMaP_TMI) are in better agreement with the PR estimates over land everywhere except over tropical Africa in the boreal summer. Validation results of the KWAJ radar and COBRA show a good linear relationship for instantaneous rainfall rates, while validation around Japan using the RA shows a good relationship in the warm season. Poor results, connected to weak-precipitation cases, are found in the cold season around Japan.
Although a high level of thymidylate synthase (TS) expression in malignant tumours has been suggested to be related to a reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for ...such an association has been demonstrated in non-small cell lung cancer (NSCLC). We have now investigated the effect of TS overexpression on pemetrexed sensitivity in NSCLC cells.
We established NSCLC cell lines that stably overexpress TS and examined the effects of such overexpression on the cytotoxicity of pemetrexed both in vitro and in xenograft models. We further examined the relation between TS expression in tumour specimens from NSCLC patients and the tumour response to pemetrexed by immunohistochemical analysis.
The sensitivity of NSCLC cells overexpressing TS to the antiproliferative effect of pemetrexed was markedly reduced compared with that of control cells. The inhibition of DNA synthesis and induction of apoptosis by pemetrexed were also greatly attenuated by forced expression of TS. Furthermore, tumours formed by TS-overexpressing NSCLC cells in nude mice were resistant to the growth-inhibitory effect of pemetrexed observed with control tumours. Finally, the level of TS expression in tumours of non-responding patients was significantly higher than that in those of responders, suggestive of an inverse correlation between TS expression and tumour response to pemetrexed.
A high level of TS expression confers a reduced sensitivity to pemetrexed. TS expression is thus a potential predictive marker for response to pemetrexed-based chemotherapy in NSCLC patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We assessed the non-inferiority of accelerated fractionation (AF) (2.4Gy/fraction) compared with standard fractionation (SF) (2Gy/fraction) regarding progression-free survival (PFS) in patients with ...T1-2N0M0 glottic cancer (GC).
In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20–80, Eastern Cooperative Oncology Group performance status of 0–1, and adequate organ function. Patients were randomly assigned to receive either SF of 66–70Gy (33–35 fractions), or AF of 60–64.8Gy (25–27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%.
Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9%(95% confidence interval CI 73.4–85.4) for SF and 81.7% (95% CI 75.4–87.0) for AF (difference 1.8%, 91% CI−5.1% to 8.8%; one-sided P=0.047>0.045). The cumulative incidences of local failure at 3years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms.
Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC.
UMIN Clinical Trial Registry, number UMIN000000819.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although ...increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated.
In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore.
ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity.
Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection.
JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Masseter muscle thickness correlates with masseter muscle echo intensity.•Masseter muscle echo intensity correlates with grip strength and walking speed.•Masseter muscle echo intensity does not ...correlate with tooth-loss.•Masseter muscle echo intensity is easily determined ultrasonographically.•Masseter muscle echo intensity may be predictive of dynapenia.
Associations between masseter muscle thickness(MMT) and limb muscle thickness, and between grip strength and MMT, as well as tooth-loss, have been reported previously. The previous study also showed that masseter muscle mass could be a better marker of sarcopenia than psoas muscle mass. Although the association between MMT and muscle strength is also known, the quality of the masseter muscle were not assessed in detail previously. We examined the relationship of masseter muscle echo intensity (MMEI) with skeletal muscle, physical function, and nutrition status, in order to determine whether MMEI could be a good indicator of these parameters.
We assessed 139 community-dwelling elderly individuals (men: 65, women: 74). Age, body mass index (BMI), skeletal muscle mass index, grip strength, walking speed, calf circumference, tooth-loss (Eichner classification), occlusal force, MMT, and MMEI were obtained. In multiple regression analysis, MMEI were set as dependent variables.
Multiple regression analysis revealed BMI (p < 0.05), grip strength (p < 0.01), walking speed (p < 0.01), and MMT (p < 0.01) as factors with significant association with MMEI.
MMT is related to occlusal force and MMEI. MMEI was related strongly to grip strength and walking speed, but not to tooth-loss. However, MMEI, which is easily determined ultrasonographically, could be a good indicator of grip strength and walking speed, and thus may be predictive of dynapenia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the ...efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC.
Patients with advanced NSCLC previously treated with≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60mg/m2 in Japan, 75mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80–120mg/day, depending on body surface area; days 1–28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2.
A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52months in the S-1 and docetaxel arms, respectively HR 0.945; 95% confidence interval (CI) 0.833–1.073; P = 0.3818. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913–1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm.
S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC.
Japan Pharmaceutical Information Center, JapicCTI-101155.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A previous randomized phase II study demonstrated that the addition of a c-Met inhibitor tivantinib to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib might prolong ...progression-free survival (PFS) in patients with previously treated, nonsquamous nonsmall-cell lung cancer (NSCLC). On a subset analysis, the survival benefit was greater in patients with wild-type EGFR (WT-EGFR) than in those with activating EGFR mutations. Herein, this phase III study compared overall survival (OS) between Asian nonsquamous NSCLC patients with WT-EGFR who received erlotinib plus tivantinib (tivantinib group) or erlotinib plus placebo (placebo group).
A total of 460 NSCLC patients were planned to be randomized to the tivantinib or placebo group. Primary end point was OS. Secondary end points were PFS, tumor response, and safety. Tissue was collected for biomarker analysis, including c-Met and HGF expression.
Enrollment was stopped when 307 patients were randomized, following the Safety Review Committee's recommendation based on an imbalance in the interstitial lung disease (ILD) incidence between the groups. ILD developed in 14 patients (3 deaths) and 6 patients (0 deaths) in the tivantinib and the placebo groups, respectively. In the enrolled patients, median OS was 12.7 and 11.1 months in the tivantinib and the placebo groups, respectively hazard ratio (HR) = 0.891, P = 0.427. Median PFS was 2.9 and 2.0 months in the tivantinib and the placebo groups, respectively (HR = 0.719, P = 0.019). The commonly observed grade ≥3 adverse events in the tivantinib group were neutropenia (24.3%), leukopenia (18.4%), febrile neutropenia (13.8%), and anemia (13.2%).
This study was prematurely terminated due to the increased ILD incidence in the tivantinib group. Although this study lacked statistical power because of the premature termination and did not demonstrate an improvement in OS, our results suggest that tivantinib plus erlotinib might improve PFS than erlotinib alone in nonsquamous NSCLC patients with WT-EGFR.
NCT01377376.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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