123 results on '"Kawakita, D"'
Search Results
2. 1580 The role of dendritic cell-regulatory T cell crosstalk in human head and neck cancer
- Author
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Minohara, K., primary, Imai, M., additional, Matoba, T., additional, Wing, J., additional, Shime, H., additional, Odanaka, M., additional, Uraki, R., additional, Kawakita, D., additional, Toyama, T., additional, Takahashi, S., additional, Morita, A., additional, Murakami, S., additional, Ohkura, N., additional, Sakaguchi, S., additional, Iwasaki, S., additional, and Yamazaki, S., additional
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- 2023
- Full Text
- View/download PDF
3. Dermopathy associated with cetuximab and panitumumab: investigation of the usefulness of moisturizers in its management
- Author
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Watanabe S, Nakamura M, Takahashi H, Hara M, Ijichi K, Kawakita D, and Morita A
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EGFR inhibitor ,moisturizer ,cetuximab ,panitumumab ,skin exsiccation ,Dermatology ,RL1-803 - Abstract
Shoichi Watanabe,1 Motoki Nakamura,1 Hiroki Takahashi,2 Masayasu Hara,2 Kei Ijichi,3 Daisuke Kawakita,3 Akimichi Morita1 1Department of Geriatric and Environmental Dermatology, 2Department of Gastroenterological Surgery, 3Department of Neuro-otolaryngology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan Aims: Limited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients. Patients and methods: Patients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid®), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms. Patients were observed for 6 weeks after the start of the administration of EGFR inhibitor. Results: A total of 15 patients were included and assessed: 6 in the prophylactic treatment group and 9 in the symptomatic treatment group. We evaluated the effect of EGFR inhibitors on the physiologic function of the skin. Administration of EGFR inhibitors resulted in a continued reduction in the moisture content of the horny layer and a decrease in cutaneous sebum levels. Skin observation revealed frequent development of an acneiform rash and significantly higher exsiccation and exfoliation scores. Administration of EGFR inhibitor was associated with a decrease in the horny layer moisture content and lower cutaneous sebum levels in the symptomatic treatment group. In contrast, levels of both the indicators were increased in the prophylactic treatment group. Moreover, the EGFR inhibitor-associated increase in exsiccation and exfoliation scores were minimized in the prophylactic treatment group relative to the symptomatic treatment group. Conclusion: Application of a moisturizer is effective against dry skin induced by the administration of an EGFR inhibitor. Keywords: EGFR inhibitor, moisturizer, colorectal cancer, head and neck cancer, prophylactical moisturizer treatment, heparinoid preparation, skin exsiccation
- Published
- 2017
4. Processed meat and risk of selected digestive tract and laryngeal cancers
- Author
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Rosato, V, Kawakita, D, Negri, E, Serraino, D, Garavello, W, Montella, M, Decarli, A, La Vecchia, C, Ferraroni, M, Rosato V., Kawakita D., Negri E., Serraino D., Garavello W., Montella M., Decarli A., La Vecchia C., Ferraroni M., Rosato, V, Kawakita, D, Negri, E, Serraino, D, Garavello, W, Montella, M, Decarli, A, La Vecchia, C, Ferraroni, M, Rosato V., Kawakita D., Negri E., Serraino D., Garavello W., Montella M., Decarli A., La Vecchia C., and Ferraroni M.
- Abstract
Background/objectives: To assess the association between processed meat and the risk of selected digestive tract and laryngeal cancers. Subjects/methods: We conducted a series of case-control studies between 1985 and 2007 in Italy. The studies included a total of 1475 cases of cancer of the oral cavity and pharynx, 1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver, 159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs), were estimated by unconditional logistic regression models, including terms for socio-demographic factors, tobacco smoking, and alcohol intake. Results: Compared to the lowest tertile of processed meat consumption, the ORs for subjects in the highest one were 1.18 (95% CI 0.98–1.43) for oral cavity and pharyngeal, 1.51 (95% CI 1.18–1.91) for esophageal, 1.19 (95% CI 0.96–1.47) for laryngeal, 0.98 (95% CI 0.81–1.18) for stomach, 0.85 (95% CI 0.51–1.40) for biliary tract, 1.20 (95% CI 0.94–1.54) for liver, and 1.46 (95% CI 1.15–1.85) for pancreatic cancers. Conclusions: Our findings support the hypothesis that high processed meat consumption increases esophageal and pancreatic cancers risk. Residual confounding by socio-demographic factors, tobacco smoking, and alcohol intake may, partly or largely, account for these associations. We found no overall association with other digestive tract and laryngeal cancers.
- Published
- 2019
5. 1126P REtrospective Study of definitive therapy for head and neck mUcosal MElanoma: The RESUME study
- Author
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Nomura, M., Kiyota, N., Shimizu, Y., Motegi, A., Akimoto, T., Mukaigawa, T., Fujii, T., Tsushima, N., Shiga, K., Koyama, T., Kawakita, D., Ohkoshi, A., Nakahira, M., Hanai, N., Murono, S., Ueda, T., Mitani, H., and Homma, A.
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- 2023
- Full Text
- View/download PDF
6. Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium
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Kawakita, D., Lee, Y. -C. A., Turati, F., Parpinel, M., Decarli, A., Serraino, D., Matsuo, K., Olshan, A. F., Zevallos, J. P., Winn, D. M., Moysich, K., Zhang, Z. -F., Morgenstern, H., Levi, F., Kelsey, K., McClean, M., Bosetti, C., Garavello, W., Schantz, S., Yu, G. -P., Boffetta, P., Chuang, S. -C., Hashibe, M., Ferraroni, M., La Vecchia, C., Edefonti, V., Kawakita, D, Lee, Y, Turati, F, Parpinel, M, Decarli, A, Serraino, D, Matsuo, K, Olshan, A, Zevallos, J, Winn, D, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Kelsey, K, Mcclean, M, Bosetti, C, Garavello, W, Schantz, S, Yu, G, Boffetta, P, Chuang, S, Hashibe, M, Ferraroni, M, La Vecchia, C, Edefonti, V, and Kawakita, D. and Lee, Y.-C.A. and Turati, F. and Parpinel, M. and Decarli, A. and Serraino, D. and Matsuo, K. and Olshan, A.F. and Zevallos, J.P. and Winn, D.M. and Moysich, K. and Zhang, Z.-F. and Morgenstern, H. and Levi, F. and Kelsey, K. and McClean, M. and Bosetti, C. and Garavello, W. and Schantz, S. and Yu, G.-P. and Boffetta, P. and Chuang, S.-C. and Hashibe, M. and Ferraroni, M. and La Vecchia, C. and Edefonti, V.
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squamous cell carcinoma ,tobacco, Adult ,Dietary Fiber ,Male ,Cancer Research ,larynx tumor ,epidemiological data ,pharynx cancer ,dietary fiber intake ,cancer risk ,Oral and gastrointestinal ,tobacco consumption ,INHANCE ,head and neck cancer ,laryngeal cancer ,oral cavity and pharyngeal cancer ,Risk Factors ,Cancer ,Head and Neck Neoplasm ,drinking behavior ,Middle Aged ,priority journal ,Oncology ,Head and Neck Neoplasms ,Adult ,Aged ,Alcohol Drinking ,Carcinoma, Squamous Cell ,Case-Control Studies ,Female ,Humans ,Laryngeal Neoplasms ,Pharyngeal Neoplasms ,Tobacco ,Case-Control Studie ,Human ,alcohol consumption ,Oncology and Carcinogenesis ,Article ,Rare Diseases ,adverse effect ,controlled study ,Pharyngeal Neoplasm ,Oncology & Carcinogenesis ,Dental/Oral and Craniofacial Disease ,Laryngeal Neoplasm ,Squamous Cell Carcinoma of Head and Neck ,Risk Factor ,Prevention ,disease association ,Carcinoma ,larynx cancer ,case control study ,mouth cancer ,major clinical study ,Good Health and Well Being ,diet therapy ,Squamous Cell ,therapeutic use ,pathology ,dietary intake ,Digestive Diseases - Abstract
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40–0.59; p for trend
- Published
- 2017
7. Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma
- Author
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Kawakita, D., Matsuo, K., Sato, F., Oze, I., Hosono, S., Ito, H., Watanabe, M., Yatabe, Y., Hanai, N., Hasegawa, Y., Tajima, K., Murakami, S., and Tanaka, H.
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- 2012
- Full Text
- View/download PDF
8. Dietary fiber intake and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology consortium
- Author
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Kawakita, D, Lee, Y, Turati, F, Parpinel, M, Decarli, A, Serraino, D, Matsuo, K, Olshan, A, Zevallos, J, Winn, D, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Kelsey, K, Mcclean, M, Bosetti, C, Garavello, W, Schantz, S, Yu, G, Boffetta, P, Chuang, S, Hashibe, M, Ferraroni, M, La Vecchia, C, Edefonti, V, Kawakita D., Lee Y. -C. A., Turati F., Parpinel M., Decarli A., Serraino D., Matsuo K., Olshan A. F., Zevallos J. P., Winn D. M., Moysich K., Zhang Z. -F., Morgenstern H., Levi F., Kelsey K., McClean M., Bosetti C., Garavello W., Schantz S., Yu G. -P., Boffetta P., Chuang S. -C., Hashibe M., Ferraroni M., La Vecchia C., Edefonti V., Kawakita, D, Lee, Y, Turati, F, Parpinel, M, Decarli, A, Serraino, D, Matsuo, K, Olshan, A, Zevallos, J, Winn, D, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Kelsey, K, Mcclean, M, Bosetti, C, Garavello, W, Schantz, S, Yu, G, Boffetta, P, Chuang, S, Hashibe, M, Ferraroni, M, La Vecchia, C, Edefonti, V, Kawakita D., Lee Y. -C. A., Turati F., Parpinel M., Decarli A., Serraino D., Matsuo K., Olshan A. F., Zevallos J. P., Winn D. M., Moysich K., Zhang Z. -F., Morgenstern H., Levi F., Kelsey K., McClean M., Bosetti C., Garavello W., Schantz S., Yu G. -P., Boffetta P., Chuang S. -C., Hashibe M., Ferraroni M., La Vecchia C., and Edefonti V.
- Abstract
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40–0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54–0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk.
- Published
- 2017
9. Global trends in nasopharyngeal cancer mortality since 1970 and predictions for 2020: Focus on low-risk areas
- Author
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Carioli, G, Negri, E, Kawakita, D, La Vecchia, C, Malvezzi, M., GARAVELLO, WERNER, G. Carioli, E. Negri, D. Kawakita, W. Garavello, C. La Vecchia, M. Malvezzi, Carioli, G, Negri, E, Kawakita, D, Garavello, W, La Vecchia, C, and Malvezzi, M
- Subjects
Adult ,Male ,Cancer Research ,Time Factors ,Time Factor ,Adolescent ,Prognosi ,nasopharyngeal cancer ,Sex Factor ,Global Health ,World Health Organization ,tobacco ,Cohort Studies ,Young Adult ,Sex Factors ,Risk Factors ,Humans ,Age Factor ,Mortality ,Child ,Aged ,Nasopharyngeal Neoplasm ,alcohol ,Risk Factor ,Medicine (all) ,Age Factors ,Infant, Newborn ,Infant ,Nasopharyngeal Neoplasms ,Middle Aged ,Prognosis ,Survival Rate ,Oncology ,Child, Preschool ,Epstein Barr viru ,Carcinoma, Squamous Cell ,Female ,Cohort Studie ,diet ,Human - Abstract
Nasopharyngeal cancer (NPC) mortality shows great disparity between endemic high risk areas, where non-keratinizing carcinoma (NKC) histology is prevalent, and non-endemic low risk regions, where the keratinizing squamous cell carcinoma (KSCC) type is more frequent. We used the World Health Organization database to calculate NPC mortality trends from 1970 to 2014 in several countries worldwide. For the European Union (EU), the United States (US) and Japan, we also predicted trends to 2020. In 2012, the highest age-standardized (world standard) rates were in Hong Kong (4.51/100,000 men and 1.15/100,000 women), followed by selected Eastern European countries. The lowest rates were in Northern Europe and Latin America. EU rates were 0.27/100,000 men and 0.09/100,000 women, US rates were 0.20/100,000 men and 0.08/100,000 women and Japanese rates were 0.16/100,000 men and 0.04/100,000 women. NPC mortality trends were favourable for several countries. The decline was −15% in men and −5% in women between 2002 and 2012 in the EU, −12% in men and −9% in women in the US and about −30% in both sexes in Hong Kong and Japan. The favourable patterns in Europe and the United States are predicted to continue. Changes in salted fish and preserved food consumption account for the fall in NKC. Smoking and alcohol prevalence disparities between sexes and geographic areas may explain the different rates and trends observed for KSCC and partially for NKC. Dietary patterns, as well as improvement in management of the disease, may partly account for the observed trends, too.
- Published
- 2016
10. Trastuzumab plus docetaxel in patients with advanced HER2-positive salivary duct carcinoma: Exploratory biomarker analyses
- Author
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Takahashi, H., primary, Kawakita, D., additional, Fushimi, C., additional, Nagao, T., additional, Hirai, H., additional, Saigusa, N., additional, Masubuchi, T., additional, Matsuki, T., additional, Okada, T., additional, Baba, D., additional, Miura, K., additional, Saotome, T., additional, and Tada, Y., additional
- Published
- 2019
- Full Text
- View/download PDF
11. Combined androgen blockade in patients with advanced androgen receptor-positive salivary gland carcinoma: Exploratory biomarker analyses
- Author
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Fushimi, C., primary, Kawakita, D., additional, Takahashi, H., additional, Nagao, T., additional, Hirai, H., additional, Saigusa, N., additional, Masubuchi, T., additional, Matsuki, T., additional, Okada, T., additional, Baba, D., additional, Miura, K., additional, Saotome, T., additional, and Tada, Y., additional
- Published
- 2019
- Full Text
- View/download PDF
12. Global trends in nasopharyngeal cancer mortality since 1970 and predictions for 2020: Focus on low-risk areas
- Author
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Carioli, G, Negri, E, Kawakita, D, Garavello, W, La Vecchia, C, Malvezzi, M, Malvezzi, M., GARAVELLO, WERNER, Carioli, G, Negri, E, Kawakita, D, Garavello, W, La Vecchia, C, Malvezzi, M, Malvezzi, M., and GARAVELLO, WERNER
- Abstract
Nasopharyngeal cancer (NPC) mortality shows great disparity between endemic high risk areas, where non-keratinizing carcinoma (NKC) histology is prevalent, and non-endemic low risk regions, where the keratinizing squamous cell carcinoma (KSCC) type is more frequent. We used the World Health Organization database to calculate NPC mortality trends from 1970 to 2014 in several countries worldwide. For the European Union (EU), the United States (US) and Japan, we also predicted trends to 2020. In 2012, the highest age-standardized (world standard) rates were in Hong Kong (4.51/100,000 men and 1.15/100,000 women), followed by selected Eastern European countries. The lowest rates were in Northern Europe and Latin America. EU rates were 0.27/100,000 men and 0.09/100,000 women, US rates were 0.20/100,000 men and 0.08/100,000 women and Japanese rates were 0.16/100,000 men and 0.04/100,000 women. NPC mortality trends were favourable for several countries. The decline was −15% in men and −5% in women between 2002 and 2012 in the EU, −12% in men and −9% in women in the US and about −30% in both sexes in Hong Kong and Japan. The favourable patterns in Europe and the United States are predicted to continue. Changes in salted fish and preserved food consumption account for the fall in NKC. Smoking and alcohol prevalence disparities between sexes and geographic areas may explain the different rates and trends observed for KSCC and partially for NKC. Dietary patterns, as well as improvement in management of the disease, may partly account for the observed trends, too.
- Published
- 2017
13. 1168P - Trastuzumab plus docetaxel in patients with advanced HER2-positive salivary duct carcinoma: Exploratory biomarker analyses
- Author
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Takahashi, H., Kawakita, D., Fushimi, C., Nagao, T., Hirai, H., Saigusa, N., Masubuchi, T., Matsuki, T., Okada, T., Baba, D., Miura, K., Saotome, T., and Tada, Y.
- Published
- 2019
- Full Text
- View/download PDF
14. 1166P - Combined androgen blockade in patients with advanced androgen receptor-positive salivary gland carcinoma: Exploratory biomarker analyses
- Author
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Fushimi, C., Kawakita, D., Takahashi, H., Nagao, T., Hirai, H., Saigusa, N., Masubuchi, T., Matsuki, T., Okada, T., Baba, D., Miura, K., Saotome, T., and Tada, Y.
- Published
- 2019
- Full Text
- View/download PDF
15. Selection of Therapeutic Treatment with Alternating Chemoradiotherapy for Larynx Preservation in Laryngeal Carcinoma Patients
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Ijichi, K., primary, Hanai, N., additional, Kawakita, D., additional, Ozawa, T., additional, Suzuki, H., additional, Hirakawa, H., additional, Kodaira, T., additional, Murakami, S., additional, and Hasegawa, Y., additional
- Published
- 2014
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16. P84. Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma
- Author
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Kawakita, D., primary, Matsuo, K., additional, Hosono, S., additional, Ito, H., additional, Hasegawa, Y., additional, and Tanaka, H., additional
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- 2011
- Full Text
- View/download PDF
17. Impact of smoking status on clinical outcome in oral cavity cancer patients.
- Author
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Kawakita D, Hosono S, Ito H, Oze I, Watanabe M, Hanai N, Hasegawa Y, Tajima K, Murakami S, Tanaka H, and Matsuo K
- Abstract
The association between smoking status and survival in oral cavity squamous cell carcinoma (OSCC) patients remains unclear. Therefore, we evaluated the association between smoking status before treatment and clinical outcome in OSCC patients. We conducted a retrospective cohort study of 222 OSCC patients who were treated at Aichi Cancer Center in Japan. Of these, 82 patients (36.9%) were non-smokers, 65 (29.3%) were light smokers (pack-years smoking (PY) <30), 54 (24.3%) were moderate smokers (30PY<60), and 21 (9.5%) were heavy smokers (60PY). The survival impact of pre-treatment smoking status was evaluated using multivariate proportional hazard models. Five-year overall survival for non-, light, moderate, and heavy smokers was 72.9% (95% confidence interval CI): (61.4-81.5), 85.5% (74.0-92.2), 59.9% (44.3-72.4) and 69.0% (42.8-85.0). Adjusted hazard ratios (HRs) for moderate and heavy smokers in comparison with light smokers were 2.44 (1.07-5.57, P=0.034) and 2.66 (0.97-7.33, P=0.058) and the dose-response relationship among smokers was statistically significance (P(trend)=0.024). In addition, adjusted HR for non-smokers relative to light smokers was 2.27 (0.84-6.15, P=0.108). We observed a suggestive heterogeneity in the impact of smoking status by treatment method (P for heterogeneity=0.069). Effect of smoking was evident only among the chemoradiotherapy or radiotherapy group. In this study, we found the significant positive dose-response relationship among smokers on clinical outcome in OSCC patients and that non-smokers were worse prognosis than light smokers. In addition, this effect might differ by treatment method. [ABSTRACT FROM AUTHOR]
- Published
- 2012
18. Orientation Dependence of Semiconductor Properties in Anatase TiO2 Polycrystalline Aggregates.
- Author
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Kawakita, Mamiko, Kawakita, D Jin, Sakka, Yoshio, and Shinohara, Tadashi
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TITANIUM dioxide crystals ,POLYCRYSTALLINE semiconductors ,ELECTROPHORETIC deposition ,SOLAR cells ,PHOTOCATALYSIS ,ELECTRIC impedance - Abstract
We investigated the effects of the crystalline orientation of anatase titanium dioxide (TiO
2 ) polycrystalline fine aggregates on semiconductor properties such as flatband potential and donor density, which affect performance in applications to dye-sensitized solar cells and photocatalysis. Aggregates with crystalline orientation were prepared through electrophoretic deposition in a strong magnetic field. Semiconductor properties were determined with Mott-Schottky plots obtained by an electrochemical impedance method. The fiatband potential of the (001)-plane perpendicular to the electrode was most negative. That of the random orientation was varied rather widely while the average value was close to that of the (001)-plane perpendicular to the electrode. The open-circuit potential of the electrode corresponding to the Fermi level of TiO2 in contact with the electrolyte tended to depend on the crystalline orientation similar to the fiatband potential. The distance between the open-circuit potential and the fiatband potential was nearly constant regardless of plane Orientation. These findings indicated that the flatband potential was controlled by Fermi-level pinning related to the surface state. Nominal donor density also depended on crystal orientation. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
19. Processed meat and risk of selected digestive tract and laryngeal cancers
- Author
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Monica Ferraroni, Diego Serraino, Carlo La Vecchia, Valentina Rosato, Eva Negri, Adriano Decarli, Werner Garavello, Maurizio Montella, Daisuke Kawakita, Rosato, V, Kawakita, D, Negri, E, Serraino, D, Garavello, W, Montella, M, Decarli, A, La Vecchia, C, Ferraroni, M, V. Rosato, D. Kawakita, E. Negri, D. Serraino, W. Garavello, M. Montella, A. Decarli, C. La Vecchia, and M. Ferraroni
- Subjects
Male ,0301 basic medicine ,Larynx ,Food Handling ,Medicine (miscellaneous) ,Digestive System Neoplasms ,Gastroenterology ,cancer of the liver ,0302 clinical medicine ,Risk Factors ,Odds Ratio ,processed meat ,risk ,Nutrition and Dietetics ,cancer of the oral cavity and pharynx ,Stomach ,Middle Aged ,Laryngeal Neoplasm ,cancer of the esophagu ,cancers of the biliary tract ,medicine.anatomical_structure ,cancer of the larynx ,Italy ,Female ,Case-Control Studie ,Human ,Adult ,medicine.medical_specialty ,Meat ,Logistic Model ,030209 endocrinology & metabolism ,03 medical and health sciences ,Internal medicine ,Digestive System Neoplasm ,medicine ,Humans ,Esophagus ,Laryngeal Neoplasms ,cancer of the stomach ,030109 nutrition & dietetics ,business.industry ,Risk Factor ,Pharynx ,Case-control study ,Cancer ,Odds ratio ,medicine.disease ,Diet ,Logistic Models ,cancer of the pancrea ,Case-Control Studies ,business - Abstract
Background/objectives: To assess the association between processed meat and the risk of selected digestive tract and laryngeal cancers. Subjects/methods: We conducted a series of case-control studies between 1985 and 2007 in Italy. The studies included a total of 1475 cases of cancer of the oral cavity and pharynx, 1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver, 159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs), were estimated by unconditional logistic regression models, including terms for socio-demographic factors, tobacco smoking, and alcohol intake. Results: Compared to the lowest tertile of processed meat consumption, the ORs for subjects in the highest one were 1.18 (95% CI 0.98–1.43) for oral cavity and pharyngeal, 1.51 (95% CI 1.18–1.91) for esophageal, 1.19 (95% CI 0.96–1.47) for laryngeal, 0.98 (95% CI 0.81–1.18) for stomach, 0.85 (95% CI 0.51–1.40) for biliary tract, 1.20 (95% CI 0.94–1.54) for liver, and 1.46 (95% CI 1.15–1.85) for pancreatic cancers. Conclusions: Our findings support the hypothesis that high processed meat consumption increases esophageal and pancreatic cancers risk. Residual confounding by socio-demographic factors, tobacco smoking, and alcohol intake may, partly or largely, account for these associations. We found no overall association with other digestive tract and laryngeal cancers.
- Published
- 2018
20. Body mass index and the risk of head and neck cancer in the Chinese population
- Author
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Jie Ma, Xiaoyan Zhou, Min Dai, Hongxia Ma, Pen Jen Lou, Wei Wu, Qian Li, Mia Hashibe, Yuji Chen, Baochang He, Wan Lun Hsu, Baosen Zhou, Yuan Chin Amy Lee, Yu Wang, Shuang Li, Hongbing Shen, Cairong Zhu, Jian Pan, Qinghai Ji, Lin Cai, Daisuke Kawakita, Zuo-Feng Zhang, Chien-Jen Chen, Paolo Boffetta, Chen Y., Lee Y.-C.A., Li S., Li Q., Chen C.-J., Hsu W.-L., Lou P.-J., Zhu C., Pan J., Shen H., Ma H., Cai L., He B., Wang Y., Zhou X., Ji Q., Zhou B., Wu W., Ma J., Kawakita D., Boffetta P., Zhang Z.-F., Dai M., and Hashibe M.
- Subjects
Adult ,Male ,Cancer Research ,Epidemiology ,Population ,Logistic regression ,Body Mass Index ,Young Adult ,03 medical and health sciences ,BMI ,0302 clinical medicine ,Asian People ,Risk Factors ,Humans ,Medicine ,030212 general & internal medicine ,education ,East Asia ,Aged ,Aged, 80 and over ,education.field_of_study ,Head and neck cancer risk ,business.industry ,Head and neck cancer ,Confounding ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Oncology ,Head and Neck Neoplasms ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Underweight ,medicine.symptom ,business ,Body mass index ,Demography - Abstract
Objective: To investigate potential associations between body mass index (BMI) and head and neck cancer (HNC) risk in an East Asian population. Methods: We conducted a hospital-based multicenter case-control study in East Asia including 921 cases and 806 controls. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CI) for HNC risks by using logistic regression, adjusting on potential confounders. Results: Compared to normal BMI at interview (18.5– 30 kg/m 2 ) was associated with a lower HNC risk (OR = 0.30, 95% CI 0.16–0.57). Being underweight at age 20 was also associated with an increased risk of HNC. However, being underweight at 5 years or 2 years before interview was not associated with a higher risk of HNC. Conclusion: We observed an inverse association between BMI and HNC risk, which is consistent with previous studies in other geographic regions. Being underweight at age 20 was also associated with a higher risk of HNC, suggesting that reverse causality was not the main source of the association.
- Published
- 2019
21. Impact of oral hygiene on head and neck cancer risk in a Chinese population
- Author
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Min Dai, Paolo Boffetta, Chien-Jen Chen, Wan Lun Hsu, Cairong Zhu, Jian Pan, Baosen Zhou, Baochang He, Yu Wang, Qinghai Ji, Lin Cai, Yuji Chen, Yuan Chin Amy Lee, Zuo-Feng Zhang, Jie Ma, Hongbing Shen, Wei Wu, Xiaoyan Zhou, Daisuke Kawakita, Hongxia Ma, Mia Hashibe, Pei-Jen Lou, Qian Li, and Kawakita, D. and Lee, Y.-C.A. and Li, Q. and Chen, Y. and Chen, C.-J. and Hsu, W.-L. and Lou, P.-J. and Zhu, C. and Pan, J. and Shen, H. and Ma, H. and Cai, L. and He, B. and Wang, Y. and Zhou, X. and Ji, Q. and Zhou, B. and Wu, W. and Ma, J. and Boffetta, P. and Zhang, Z.-F. and Dai, M. and Hashibe, M.
- Subjects
squamous cell carcinoma ,Male ,cancer patient ,very elderly ,ICD-O-3 ,Dentistry ,cancer risk ,Logistic regression ,Oral and gastrointestinal ,0302 clinical medicine ,Odds Ratio ,80 and over ,Medicine ,030212 general & internal medicine ,tooth ,multivariate analysi ,comparative study ,risk ,Cancer ,Aged, 80 and over ,Head and Neck Neoplasm ,Incidence ,Confounding ,drinking behavior ,clinical trial ,Middle Aged ,medical history ,priority journal ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Asian population ,Carcinoma, Squamous Cell ,Female ,Case-Control Studie ,Human ,Adult ,medicine.medical_specialty ,China ,Logistic Model ,mastication ,Clinical Sciences ,betel quid ,dental prophylaxi ,Oral hygiene ,Risk Assessment ,smoking ,Article ,young adult, Adult ,03 medical and health sciences ,Young Adult ,Age Distribution ,Rare Diseases ,Clinical Research ,Internal medicine ,Confidence Intervals ,Humans ,controlled study ,Neoplasm Invasiveness ,Poor oral hygiene ,Sex Distribution ,Dental/Oral and Craniofacial Disease ,Neoplasm Staging ,Aged ,head and neck tumor ,Neoplasm Invasivene ,Chinese population ,Chinese ,business.industry ,Taiwanese ,cancer staging ,Prevention ,statistical model ,Head and neck cancer ,Carcinoma ,oral hygiene ,mouth hygiene ,Odds ratio ,case control study ,sex ratio ,tumor invasion ,medicine.disease ,Oral Hygiene ,major clinical study ,stomatognathic diseases ,multicenter study ,Logistic Models ,confidence interval ,Squamous Cell ,Otorhinolaryngology ,Case-Control Studies ,Multivariate Analysis ,pathology ,dental care ,head and neck cancer ,business - Abstract
Background: Although the impact of oral hygiene on head and neck cancer risk has been investigated, few studies have been conducted among the Asian population. Methods: We conducted a multicenter case-control study to investigate this potential association. We performed unconditional multiple logistic regression models adjusted by potential confounders. Results: We observed an inverse association of frequency of dental visits with head and neck cancer risk, with an adjusted odds ratio (OR) of 3.70 (95% CI 2.51-5.45) for never dental visits compared with ≥1 time/year (Ptrend
- Published
- 2017
22. Clinical benefits of combining oral cytotoxic chemotherapeutic agents with radiotherapy in patients with T2N0 glottic squamous cell carcinoma based on the reports of the Head and Neck Cancer Registry of Japan.
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Ichisaka T, Sano D, Kijima N, Kawakita D, Yoshimoto S, Kitayama M, Nibu KI, and Oridate N
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- Humans, Male, Female, Japan, Aged, Middle Aged, Retrospective Studies, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell radiotherapy, Carcinoma, Squamous Cell drug therapy, Administration, Oral, Antineoplastic Agents therapeutic use, Antineoplastic Agents administration & dosage, Squamous Cell Carcinoma of Head and Neck therapy, Squamous Cell Carcinoma of Head and Neck pathology, Squamous Cell Carcinoma of Head and Neck mortality, Squamous Cell Carcinoma of Head and Neck radiotherapy, Squamous Cell Carcinoma of Head and Neck drug therapy, Head and Neck Neoplasms therapy, Head and Neck Neoplasms radiotherapy, Head and Neck Neoplasms pathology, Head and Neck Neoplasms mortality, Adult, Aged, 80 and over, Chemoradiotherapy methods, Laryngeal Neoplasms therapy, Laryngeal Neoplasms pathology, Laryngeal Neoplasms radiotherapy, Laryngeal Neoplasms mortality, Registries, Glottis pathology
- Abstract
Background: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC., Methods: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics., Results: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026)., Conclusions: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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23. The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma.
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Kajiwara M, Takahashi H, Nakaguro M, Kawakita D, Hirai H, Utsumi Y, Urano M, Sato Y, Tsukahara K, Kano S, Okami K, Ozawa H, Yamazaki K, Okada T, Shimizu A, Hanyu K, Sakai A, Yamauchi M, Sekimizu M, Hanazawa T, Saito Y, Ueki Y, Honma Y, Arai T, Iwaki S, Yamamura K, Imanishi Y, Sato Y, Tada Y, and Nagao T
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- Humans, Male, Female, Middle Aged, Aged, Adult, Prognosis, Aged, 80 and over, Biomarkers, Tumor analysis, Biomarkers, Tumor metabolism, Salivary Ducts pathology, Salivary Ducts innervation, Vesicular Acetylcholine Transport Proteins metabolism, Tyrosine 3-Monooxygenase metabolism, Tyrosine 3-Monooxygenase analysis, Immunohistochemistry, Autonomic Pathways pathology, Autonomic Nervous System pathology, Autonomic Nervous System metabolism, Carcinoma, Ductal pathology, S100 Proteins metabolism, S100 Proteins analysis, Tumor Microenvironment, Salivary Gland Neoplasms pathology, Salivary Gland Neoplasms metabolism
- Abstract
Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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24. Comprehensive genomic profiling of salivary gland carcinoma: Analysis of the Center for Cancer Genomics and Advanced Therapeutics database in Japan.
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Iwaki S, Kawakita D, Nagao T, Tada Y, Honma Y, Ando M, Matoba T, Minohara K, Nakano S, Murase T, Iwasaki S, and Inagaki H
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- Humans, Male, Female, Japan epidemiology, Aged, Middle Aged, Adult, Receptor, ErbB-2 genetics, Aged, 80 and over, Genomics methods, Cyclin-Dependent Kinase Inhibitor p16 genetics, Tumor Suppressor Protein p53 genetics, Carcinoma, Adenoid Cystic genetics, Carcinoma, Adenoid Cystic pathology, Databases, Genetic, Carcinoma, Ductal genetics, Carcinoma, Ductal pathology, Carcinoma, Ductal therapy, Proto-Oncogene Proteins B-raf genetics, Young Adult, Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma therapy, Salivary Gland Neoplasms genetics, Salivary Gland Neoplasms pathology, Salivary Gland Neoplasms therapy
- Abstract
Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C-CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC., (© 2024 UICC.)
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- 2024
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25. PD-L1 expression as a predictive biomarker in patients with recurrent or metastatic salivary gland carcinoma treated with pembrolizumab.
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Matsuki T, Kawakita D, Takahashi H, Okada T, Sakai A, Ueki Y, Tsuge H, Hanyu K, Momiyama K, Shodo R, Yamauchi M, Asako Y, Hirai H, Nagao T, and Tada Y
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- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Adult, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Prognosis, Neoplasm Metastasis, Antineoplastic Agents, Immunological therapeutic use, Aged, 80 and over, Treatment Outcome, Progression-Free Survival, Antibodies, Monoclonal, Humanized therapeutic use, Salivary Gland Neoplasms drug therapy, Salivary Gland Neoplasms pathology, Salivary Gland Neoplasms metabolism, Salivary Gland Neoplasms mortality, B7-H1 Antigen metabolism, Biomarkers, Tumor metabolism
- Abstract
Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS., (© 2024. The Author(s).)
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- 2024
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26. Impact of salvage chemotherapy after immune checkpoint inhibitor for recurrent or metastatic head and neck cancer.
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Matoba T, Minohara K, Kawakita D, Sawabe M, Takano G, Oguri K, Murashima A, Iwaki S, Tsuge H, Imaizumi S, Hojo W, Kondo A, Tsukamoto K, and Iwasaki S
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- Humans, Male, Middle Aged, Female, Aged, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Adult, Cetuximab therapeutic use, Progression-Free Survival, Salvage Therapy, Immune Checkpoint Inhibitors therapeutic use, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Head and Neck Neoplasms therapy, Neoplasm Recurrence, Local drug therapy, Paclitaxel therapeutic use, Paclitaxel administration & dosage
- Abstract
Background: It is unclear witch regimen is optimal as salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) monotherapy for recurrent or metastatic head and neck cancer (RM-HNC)., Methods: This study enrolled 109 patients. Overall survival (OS) and progression-free survival 2 (PFS2) were compared between patients stratified by SCT regimen., Results: Of the 109 patients, 55 underwent SCT after the failure of ICI monotherapy. The OS of these 55 patients was longer than that of patients who did not undergo SCT. The OS and PFS2 were similar between patients treated with paclitaxel (PTX) and cetuximab (Cmab) combination and those treated with PTX monotherapy. The occurrence of irAEs did not impact PFS2 nor OS., Conclusions: SCT can improve the survival outcomes of patients with RM-HNC. In addition to PTX and Cmab, PTX monotherapy is also considered an effective SCT regimen. SCT is effective regardless of the presence or absence of irAEs., (© 2024 Wiley Periodicals LLC.)
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- 2024
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27. Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.
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Tasaki Y, Ito N, Mimura Y, Sugiyama Y, Ogawa R, Shimura T, Nakamura M, Kawakita D, Hamamoto S, Uemura T, Yokota K, Iida M, Odagiri K, Kimura Y, Hotta Y, Komatsu H, Okuda K, Niimi A, Yasui T, Iwasaki S, Morita A, Kataoka H, Takiguchi S, and Furukawa-Hibi Y
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Drug Administration Schedule, East Asian People, Japan, Retrospective Studies, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological economics, Neoplasms drug therapy, Neoplasms economics, Nivolumab administration & dosage, Nivolumab economics
- Abstract
Aim: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer., Methods: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group)., Results: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥ grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥ grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05)., Conclusion: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact., (© 2024 John Wiley & Sons Australia, Ltd.)
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- 2024
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28. Survival Outcome Superiority of Total Pharyngolaryngectomy Compared with Chemoradiotherapy for T4aM0 Hypopharyngeal Squamous Cell Carcinoma: A Nationwide Database Study of Japan.
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Omura G, Eguchi K, Yoshimoto S, Honma Y, Fushimi C, Sakai T, Matsumoto Y, Sakai A, Kitayama M, Kawakita D, Kirita T, Kodaira T, Nakamizo M, and Nibu KI
- Subjects
- Humans, Male, Female, Survival Rate, Aged, Middle Aged, Japan epidemiology, Prognosis, Follow-Up Studies, Neoplasm Staging, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Hypopharyngeal Neoplasms therapy, Hypopharyngeal Neoplasms mortality, Hypopharyngeal Neoplasms pathology, Pharyngectomy, Chemoradiotherapy mortality, Laryngectomy mortality, Databases, Factual
- Abstract
Background: The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database., Methods: All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses., Results: Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively)., Conclusions: Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT., (© 2024. Society of Surgical Oncology.)
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- 2024
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29. Clinical impact of hyperbaric oxygen therapy combined with steroid treatment for sudden sensorineural hearing loss: A case-control study.
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Sanda N, Sawabe M, Kabaya K, Kawaguchi M, Fukushima A, Nakamura Y, Maseki S, Niwa M, Mori H, Hyodo Y, Nishiyama K, Kawakita D, and Iwasaki S
- Abstract
Objectives: The aim of present study was to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBOT) as a primary therapy combined with standard systemic corticosteroid treatment for sudden sensorineural hearing loss (SSNHL) compared to treatment without the use of HBOT (non-HBOT) through clinical data and advanced analytical approaches., Study Design: Case-control study., Methods: Conducted across three Japanese medical centers involving 298 SSNHL patients diagnosed between 2020 and 2023. Inclusion criteria encompassed first onset and treatment, WHO grade 3 or 4 initial hearing impairment, receipt of systemic corticosteroid therapy within 14 days of symptom onset, and initiation of HBOT within the same timeframe for the case group. The primary outcome measure was the difference in hearing improvement (mean hearing level in decibels, dB) between the two groups, assessed by pure-tone audiometry at baseline and 3 months post-treatment, using the inverse probability of treatment weighting (IPTW) method adjusted for covariate differences., Results: The study included 67 patients in the HBOT group and 68 in the non-HBOT group. The HBOT group exhibited significantly greater hearing improvement (IPTW-adjusted difference: 7.6 dB, 95% CI 0.4-14.7; p = 0.038). Patients without vertigo in the HBOT group demonstrated substantial hearing improvement (11.5 dB, 95% CI 2.3-20.6; p = 0.014), whereas those with vertigo showed no significant improvement (-1.8 dB, 95% CI -11.8-8.3; p = 0.729). The HBOT group also had a significantly higher association with complete recovery (IPTW-adjusted odds ratio: 2.57, 95% CI 1.13-5.85; p = 0.025)., Conclusion: In SSHNL, HBOT combination therapy yielded slightly but significantly improved hearing outcomes compared to non-HBOT treatment., Level of Evidence: 4., Competing Interests: The authors declare that they have no conflict of interest and source of funding., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)
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- 2024
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30. [Ⅳ. HPV Vaccines in Head and Neck Cancer Prevention].
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Yasuda K and Kawakita D
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- Humans, Papillomavirus Vaccines administration & dosage, Papillomavirus Vaccines immunology, Head and Neck Neoplasms prevention & control, Head and Neck Neoplasms immunology, Papillomavirus Infections prevention & control, Papillomavirus Infections complications
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- 2024
31. Survival impact of sequential chemotherapy following pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.
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Iwaki S, Kadowaki S, Honda K, Narita Y, Masuishi T, Taniguchi H, Ando M, Muro K, Sawabe M, Suzuki H, Nishikawa D, Beppu S, Terada H, Kishikawa T, Kawakita D, and Hanai N
- Subjects
- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Adult, Progression-Free Survival, Aged, 80 and over, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck mortality, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Neoplasm Recurrence, Local drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: Pembrolizumab alone or combined with chemotherapy is the standard of care for first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with positive programmed death-ligand 1 combined positive scores. However, data on second-line chemotherapy following pembrolizumab are scarce., Methods: A single-center, retrospective study was conducted to determine the efficacies of pembrolizumab and pembrolizumab plus chemotherapy as first-line treatments and the efficacy of second-line chemotherapy for patients with R/M HNSCC who were refractory or intolerant to first-line treatment., Results: Fifty-four patients were treated with pembrolizumab, and 29 received second-line therapy, with 27 opting for cetuximab-containing regimens. The median progression-free survival (PFS), overall survival (OS), and PFS on next-line therapy for first-line treatment were 4.7 (95% confidence interval [CI], 2.1-8.7), 22.1 (95% CI, 12.6-not reached), and 15.6 months (95% CI, 9.7-not reached) in the pembrolizumab group and 5.4 (95% CI, 3.3-6.8), 15.8 (95% CI, 8.6-not reached), and 13.7 months (95% CI, 8.1-not reached) in the pembrolizumab plus chemotherapy group, respectively. The overall response rate and median PFS for second-line treatment were 48.3% (95% CI, 30.4-67.0) and 6.1 months (95% CI, 2.30-8.84). The median OS for patients who received second-line treatment was 18.4 months, which was superior to the median OS of 6.0 months for patients who received the best supportive care (log-rank p = 0.10)., Conclusion: This study indicates that cetuximab-containing second-line chemotherapy can improve outcomes in R/M HNSCC, even after first-line therapy failure or intolerance., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2024
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32. Brain metastases in patients with salivary duct carcinoma: A retrospective study.
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Fushimi C, Takahashi H, Kawakita D, Kano S, Tsukahara K, Ozawa H, Okami K, Sakai A, Yamazaki K, Okada T, Hanazawa T, Sato Y, Imanishi Y, Shimizu A, Matsuki T, Nagao T, and Tada Y
- Subjects
- Humans, Retrospective Studies, Salivary Ducts pathology, Prognosis, Salivary Gland Neoplasms pathology, Carcinoma, Ductal pathology, Brain Neoplasms pathology
- Abstract
Background: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses., Methods: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication., Results: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001)., Conclusion: The SDC-GPA score emerged as a useful prognostication tool for patients with BM., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2024
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33. Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.
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Yasuda K, Uchinami Y, Kano S, Taguchi J, Kawakita D, Kitayama M, Nishioka K, Mori T, Koizumi F, Fujii Y, Shimizu Y, Kobashi K, Yoshimoto S, Nibu KI, Homma A, and Aoyama H
- Subjects
- Aged, Humans, Japan, Chemoradiotherapy, Registries, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy
- Abstract
Background: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan., Methods: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included., Results: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05)., Conclusion: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2024
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34. Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.
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Tsuge H, Kawakita D, Taniyama Y, Oze I, Koyanagi YN, Hori M, Nakata K, Sugiyama H, Miyashiro I, Oki I, Nishino Y, Katanoda K, Ito Y, Shibata A, Matsuda T, Iwasaki S, Matsuo K, and Ito H
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- Humans, Japan epidemiology, Prognosis, Carcinoma, Squamous Cell, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms therapy, Laryngeal Neoplasms
- Abstract
Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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- 2024
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35. Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.
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Homma A, Ando M, Hanai N, Harada H, Honma Y, Kanda T, Kano S, Kawakita D, Kiyota N, Kizawa Y, Nakagawa M, Ogawa T, Shinomiya H, Shinozaki T, Suzuki M, Tsuji T, Yasuda K, Zenda S, Kodaira T, Kirita T, and Nibu KI
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- Humans, Japan, Practice Guidelines as Topic, Head and Neck Neoplasms therapy
- Abstract
The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments., (Copyright © 2023. Published by Elsevier B.V.)
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- 2024
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36. Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.
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Koide Y, Kodaira T, Kitayama M, Kawakita D, Kirita T, Yoshimoto S, Nakamizo M, and Nibu KI
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- Humans, Male, Middle Aged, Female, Nasopharyngeal Carcinoma radiotherapy, Japan epidemiology, Neoplasm Staging, Chemoradiotherapy methods, Registries, Retrospective Studies, Head and Neck Neoplasms pathology, Radiotherapy, Intensity-Modulated methods, Nasopharyngeal Neoplasms pathology
- Abstract
Objective: This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data., Methods: A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage., Results: A total of 457 patients met the inclusion criteria. The median age was 60 years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively., Conclusions: This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
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- 2024
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37. Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.
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Tasaki Y, Sugiyama Y, Hamamoto S, Naiki T, Uemura T, Yokota K, Kawakita D, Nakamura M, Ogawa R, Shimura T, Mimura Y, Hotta Y, Odagiri K, Ito N, Iida M, Kimura Y, Komatsu H, Kataoka H, Takiguchi S, Morita A, Iwasaki S, Okuda K, Niimi A, Yasui T, and Furukawa-Hibi Y
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- Humans, Immune Checkpoint Inhibitors adverse effects, Eosinophils, Retrospective Studies, Biomarkers, Melanoma drug therapy
- Abstract
Background: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs., Methods: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment., Results: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67)., Conclusion: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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38. The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer.
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Sawabe M, Kawakita D, Oze I, Iwasaki S, Hasegawa Y, Murakami S, Ito H, Hanai N, and Matsuo K
- Abstract
Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HR
T3-T1 ) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1 : 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.- Published
- 2023
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39. Dosimetric and radiobiological analyses of a de-escalation strategy for elective nodal regions in human papillomavirus-associated oropharyngeal cancer.
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Tomita N, Hayashi N, Mizuno T, Kitagawa Y, Yasui K, Saito Y, Sudo S, Takano S, Kita N, Torii A, Niwa M, Okazaki D, Takaoka T, Kawakita D, Iwasaki S, and Hiwatashi A
- Abstract
Introduction: In this simulation study, we examined the effects of a de-escalation strategy with a reduced dose to subclinical nodal regions in patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC)., Methods: We created two patterns of intensity-modulated radiotherapy for 16 patients with HPV-associated OPC. In the standard and de-escalation plans, the initial field including elective nodal regions received 46 and 30 Gy, followed by 20 and 36 Gy to the cutdown field, respectively. Comparison metrics were set for each organ at risk (OAR). We compared these metric values and the probability of adverse effects based on the normal tissue complication probability (NTCP) model between the two plans., Results: Both plans generally met the dose constraints for the targets and all OAR. Among the comparison metrics, the mean doses to the brain, pharyngeal constrictor muscle, thyroid, and skin and the dose to a 1 % volume of the skin were higher in the standard plan than in the de-escalation plan ( P = 0.031, 0.007, < 0.001, < 0.001, and 0.006, respectively). NTCP analyses revealed that the probability of adverse effects in the ipsilateral parotid gland and thyroid was higher in the standard plan than in the de-escalation plan (standard vs. de-escalation plans: ipsilateral parotid gland, 6.4 % vs. 5.0 %, P = 0.016; thyroid, 3.3 % vs. 0.5 %, P < 0.001)., Conclusions: A de-escalation strategy with elective nodal regions is a promising treatment to prevent a decline in the quality of life in patients with HPV-associated OPC, particularly xerostomia, dysphagia, and hypothyroidism., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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40. The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.
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Ueda K, Murase T, Kawakita D, Nagao T, Kusafuka K, Nakaguro M, Urano M, Yamamoto H, Taguchi KI, Kano S, Tada Y, Tsukahara K, Okami K, Onitsuka T, Fujimoto Y, Sakurai K, Hanai N, Nagao T, Kawata R, Hato N, Nibu KI, and Inagaki H
- Abstract
Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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41. Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis.
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Shimoda H, Teshima M, Murase T, Nagao T, Kusafuka K, Nakaguro M, Urano M, Taguchi KI, Yamamoto H, Kano S, Tada Y, Tsukahara K, Okami K, Onitsuka T, Fujimoto Y, Kawakita D, Sakurai K, Hanai N, Nagao T, Kawata R, Hato N, Nibu KI, and Inagaki H
- Subjects
- Humans, Lymphatic Metastasis pathology, Prognosis, Margins of Excision, Neoplasm Recurrence, Local pathology, Lymph Nodes pathology, Retrospective Studies, Neoplasm Staging, Carcinoma, Adenoid Cystic pathology, Salivary Gland Neoplasms pathology
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Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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42. Importance of the Number and Location of Lymph Node Metastasis in Oropharyngeal Cancer.
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Iida M, Murai T, Kuno M, Osumi K, Nakanishi-Imai M, Okazaki D, Murase T, Kawakita D, Iwasaki S, Inagaki H, Tomita N, Shibamoto Y, and Hiwatashi A
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- Humans, Lymphatic Metastasis pathology, Neoplasm Staging, Proportional Hazards Models, Prognosis, Retrospective Studies, Lymph Nodes pathology, Oropharyngeal Neoplasms radiotherapy, Papillomavirus Infections complications
- Abstract
Background/aim: The 8
th edition of the American Joint Committee on Cancer staging system classifies oropharyngeal cancer (OPC) by the expression of p16. The discrepancy observed in this system between pathological and clinical N-stages in p16-positive OPC has provoked controversy. Therefore, this study investigated prognostic factors not included in the new staging system for p16-positive OPC patients., Patients and Methods: Patients with non-metastatic OPC receiving radiotherapy were reviewed. Clinical lymph node statuses were reassessed based on contrast-enhanced computed tomography and fluorodeoxyglucose positron emission tomography. Overall survival (OS) and cause-specific survival (CSS) were analyzed using multivariate analyses to adjust baseline imbalances., Results: In total, 166 OPC patients were reviewed. Among them, 81 patients with p16-positive were analyzed. Three or more lymph node metastases (LNM) were observed in 21 p16-positive OPCs. Retropharyngeal lymph node metastasis (Rp) was found in 12. Three-year OS, CSS, and progression-free survival rates in p16-positive patients were 76, 88, and 81%, respectively. In multivariate analyses of p16-positive OPC, LNM ≥3 was a prognostic factor of OS (hazard ratio=9.30, p<0.001) and CSS (hazard ratio=17.80, p=0.005). Rp was associated with poor CSS (hazard ratio=8.73, p=0.03). In N0-1 p16-positive patients, LNM ≥3 trended to be associated with poor OS (hazard ratio=3.93, p=0.06). CSS in patients with Rp was unfavorable (hazard ratio=70.16, p=0.05)., Conclusion: LNM ≥3 and Rp may be predictive of OS and CCS in p16-positive OPC. These are also possibly used to subcategorize p16-positive cN0-1 OPC. Further validation of lymph node staging is needed to refine the clinical staging system., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2023
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43. Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.
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Hirai H, Nakaguro M, Tada Y, Saigusa N, Kawakita D, Honma Y, Kano S, Tsukahara K, Ozawa H, Okada T, Okami K, Yamazaki K, Sato Y, Urano M, Kajiwara M, Utsumi Y, Shimura T, Fushimi C, Shimizu A, Kondo T, Imanishi Y, Sakai A, Sato Y, Togashi T, Hanazawa T, Matsuki T, Yamazaki K, and Nagao T
- Subjects
- Humans, B7-H1 Antigen metabolism, CTLA-4 Antigen, Prognosis, Salivary Ducts metabolism, Lymphocytes, Tumor-Infiltrating, Microsatellite Instability, Forkhead Transcription Factors metabolism, Tumor Microenvironment, Salivary Gland Neoplasms pathology, Carcinoma pathology
- Abstract
Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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44. Predictive factors for dissection-free sentinel node micrometastases in early oral squamous cell carcinoma.
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Matsuzuka T, Tsukahara K, Yoshimoto S, Chikamatsu K, Shiotani A, Oze I, Murakami Y, Shinozaki T, Enoki Y, Ohba S, Kawakita D, Hanai N, Koide Y, Sawabe M, Nakata Y, Fukuda Y, Nishikawa D, Takano G, Kimura T, Oguri K, Hirakawa H, and Hasegawa Y
- Subjects
- Humans, Squamous Cell Carcinoma of Head and Neck pathology, Neoplasm Micrometastasis pathology, Retrospective Studies, Neoplasm Staging, Sentinel Lymph Node Biopsy, Lymph Node Excision, Lymph Nodes pathology, Carcinoma, Squamous Cell surgery, Carcinoma, Squamous Cell pathology, Mouth Neoplasms surgery, Mouth Neoplasms pathology, Head and Neck Neoplasms pathology
- Abstract
This sentinel node (SN) biopsy trial aimed to assess its effectiveness in identifying predictive factors of micrometastases and to determine whether elective neck dissection is necessary in oral squamous cell carcinoma. This retrospective study included 55 patients from three previous trials, with positive SNs. The relationship between the sizes of the metastatic focus and metastasis in non-sentinel node (NSN) was investigated. Four of the 55 largest metastatic focus were isolated tumor cells, and the remaining 51 were ranged from 0.2 to 15 mm, with a median of 2.6 mm. The difference of prevalence between 46 negative- and 9 positive-NSN was statistically significant with regard to age, long diameter of primary site and number of cases with regional recurrence. In comparing the size of largest metastatic focus dividing the number of positive SN, with metastaic focus range of < 3.0 mm in one-positive SN group, there were 18 (33%) negative-NSN and no positive-NSN. Regarding prognosis, 3-year overall survival rate of this group (n = 18) and other (n = 37) were 94% and 73% (p = 0.04), and 3-year recurrence free survival rate of this group and other were 94% and 51% (p = 0.03), respectively. Absolutely a further prospective clinical trial would be needed, micrometastases may be defined as solitary SN metastasis with < 3.0 mm of metastatic focus, and approximately 33% of neck dissections could be avoided using these criteria., (© 2023. The Author(s).)
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- 2023
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45. Mature dendritic cells enriched in regulatory molecules may control regulatory T cells and the prognosis of head and neck cancer.
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Minohara K, Imai M, Matoba T, Wing JB, Shime H, Odanaka M, Uraki R, Kawakita D, Toyama T, Takahashi S, Morita A, Murakami S, Ohkura N, Sakaguchi S, Iwasaki S, and Yamazaki S
- Subjects
- Humans, Squamous Cell Carcinoma of Head and Neck metabolism, CD8-Positive T-Lymphocytes, Prognosis, Dendritic Cells, Tumor Microenvironment, T-Lymphocytes, Regulatory, Head and Neck Neoplasms genetics, Head and Neck Neoplasms metabolism
- Abstract
We previously reported that regulatory T (Treg) cells expressing CTLA-4 on the cell surface are abundant in head and neck squamous cell carcinoma (HNSCC). The role of expanded Treg cells in the tumor microenvironment of HNSCC remains unclear. In this study, we reveal that the tumor microenvironment of HNSCC is characterized by the high expression of genes related to Treg cells, dendritic cells (DCs), and interleukin (IL)-17-related molecules. Increased expression of IL17A, IL17F, or IL23A contributes to a favorable prognosis of HNSCC. In the tumor microenvironment of HNSCC, IL23A and IL12B are expressed in mature dendritic cells enriched in regulatory molecules (mregDCs). The mregDCs in HNSCC are a migratory and mature phenotype; their signature genes strongly correlate with Treg signature genes in HNSCC. We also observed that IL17A was highly expressed in Th17 cells and exhausted CD8
+ T cells in HNSCC. These data suggest that mregDCs in HNSCC may contribute to the prognosis by balancing Treg cells and effector T cells that produce IL-17. Targeting mregDCs may be a novel strategy for developing new immune therapies against HNSCC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2023
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46. Macroscopic and multiple metastases in sentinel lymph node biopsy are respectively associated with poor prognosis in early oral cancer.
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Kondo T, Tsukahara K, Kawakita D, Yoshimoto S, Miura K, Sugasawa M, Chikamatsu K, Matsuzuka T, Oze I, Kitamura M, Murakami Y, Otozai S, Shinozaki T, Ohba S, Araki K, Mizumachi T, Sato D, Wakisaka N, Hirakawa H, and Hasegawa Y
- Subjects
- Humans, Female, Sentinel Lymph Node Biopsy, Lymphatic Metastasis pathology, Neck Dissection, Disease-Free Survival, Lymph Nodes surgery, Lymph Nodes pathology, Mouth Neoplasms surgery, Mouth Neoplasms pathology, Sentinel Lymph Node surgery, Sentinel Lymph Node pathology, Breast Neoplasms pathology
- Abstract
Background: A multicenter, randomized controlled phase III trial was conducted on sentinel lymph node biopsy (SLNB) and elective neck dissection for T1 (depth of invasion ≥ 4 mm)-T2N0M0 oral cavity squamous cell carcinoma. This study identified factors associated with poor prognosis in patients who underwent SLNB based on a subgroup analysis of this trial., Methods: We analyzed 418 sentinel lymph nodes (SLNs) from 132 patients who underwent SLNB. The metastatic SLNs were classified into three categories based on size-isolated tumor cells: < 0.2 mm, micrometastasis: ≥ 0.2 mm and < 2 mm, and macrometastasis: ≥ 2 mm. Three groups were formed based on the number of metastatic SLNs: no metastasis, 1 metastatic node, and ≥ 2 metastatic nodes. The size and number of metastatic SLNs on survival were evaluated using Cox proportional hazard models., Results: Patients with macrometastasis and ≥ 2 metastatic SLNs had worse overall survival (OS) and disease-free survival (DFS) after adjustment for potential confounders (HR for OS: macrometastasis, 4.85; 95% CI 1.34-17.60; ≥ 2 metastatic SLN, 3.63; 95% CI 1.02-12.89; HR for DFS: macrometastasis, 2.94; 95% CI 1.16-7.44; ≥ 2 metastatic SLN, 2.97; 95% CI 1.18-7.51)., Conclusions: In patients who underwent SLNB, a poorer prognosis was associated with macrometastasis or having ≥ 2 metastatic SLNs., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
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- 2023
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47. Long-term efficacy of weekly paclitaxel therapy in unresectable primary squamous cell carcinoma of the thyroid.
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Iwaki S, Kawakita D, Sawabe M, Matoba T, Takano G, Oguri K, Murashima A, Minohara K, Tanaka N, Tsuge H, Imaizumi S, Matsumura A, Masaki A, Murase T, Ogawa M, and Iwasaki S
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Preschool, Female, Humans, Paclitaxel, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell pathology, Thyroid Neoplasms diagnostic imaging, Thyroid Neoplasms drug therapy, Thyroid Neoplasms pathology
- Abstract
Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare disease with a poor prognosis. Because of its rarity, there is no established therapeutic regimen in unresectable cases. We report a case of PSCCT treated with weekly paclitaxel (wPTX) for more than 2 years. A 59-year-old woman presented to our hospital with a progressively enlarging neck mass. CT and MRI scans showed a tumor arising from the right lobe of the thyroid, invading the esophagus and trachea, as well as partially surrounding and invading the right common carotid artery. It was deemed unresectable. Biopsy revealed poorly differentiated squamous cell carcinoma. wPTX therapy was initiated. The patient achieved a partial response and is still undergoing treatment 28 months later. Adverse events included grade 3 neutropenia and grade 2 peripheral sensory neuropathy, which were manageable. Long-term wPTX therapy has been effective in this case of unresectable PSCCT., (Copyright © 2021. Published by Elsevier B.V.)
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- 2022
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48. Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling.
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Kohsaka S, Tada Y, Ando M, Nakaguro M, Shirai Y, Ueno T, Kojima S, Hirai H, Saigusa N, Kano S, Tsukahara K, Togashi T, Ozawa H, Kondo T, Okami K, Takahashi H, Kawakita D, Fushimi C, Suzuki T, Shimizu A, Okamoto I, Okada T, Sato Y, Imanishi Y, Watanabe Y, Sakai A, Ebisumoto K, Sato Y, Urano M, Honma Y, Yamazaki K, Ueki Y, Hanazawa T, Saito Y, Shimura T, Nagao T, and Mano H
- Abstract
Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73-13.1, p = 7.8 × 10
-6 ). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies., (© 2022. The Author(s).)- Published
- 2022
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49. Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma.
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Kawakita D, Nagao T, Takahashi H, Kano S, Honma Y, Hirai H, Saigusa N, Akazawa K, Tani K, Ojiri H, Tsukahara K, Ozawa H, Okami K, Kondo T, Togashi T, Fushimi C, Shimura T, Shimizu A, Okamoto I, Okada T, Imanishi Y, Watanabe Y, Otsuka K, Sakai A, Ebisumoto K, Sato Y, Yamazaki K, Ueki Y, Hanazawa T, Saito Y, Ando M, Matsuki T, Nakaguro M, Sato Y, Urano M, Utsumi Y, Kohsaka S, Saotome T, and Tada Y
- Abstract
Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown., Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC., Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB., Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT., Competing Interests: Competing interests: The authors declare that there is no conflict of interest., (© The Author(s), 2022.)
- Published
- 2022
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50. Impact of tumor burden on survival in patients with recurrent or metastatic head and neck cancer treated with immune checkpoint inhibitors.
- Author
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Matoba T, Minohara K, Kawakita D, Takano G, Oguri K, Murashima A, Nakai K, Iwaki S, Tsuge H, Tanaka N, Imaizumi S, Hojo W, Matsumura A, Tsukamoto K, Esaki S, and Iwasaki S
- Subjects
- Humans, Immune Checkpoint Inhibitors therapeutic use, Neoplasm Recurrence, Local chemically induced, Neoplasm Recurrence, Local drug therapy, Retrospective Studies, Tumor Burden, Antineoplastic Agents, Immunological, Carcinoma, Non-Small-Cell Lung pathology, Head and Neck Neoplasms drug therapy, Lung Neoplasms pathology
- Abstract
Immune checkpoint inhibitors (ICIs) have become the standard treatment for recurrent or metastatic head and neck cancer (RM-HNC). However, many patients fail to benefit from the treatment. Previous studies have revealed that tumor burden predicts the efficacy of ICIs, but this association remains unclear for RM-HNC. We retrospectively analyzed 94 patients with RM-HNC treated with ICI monotherapy. We estimated the tumor burden using the baseline number of metastatic lesions (BNML) and the baseline sum of the longest diameters of the target lesions (BSLD), and evaluated the association between BNML, BSLD, and standardized uptake value (SUV) and clinical outcomes. The median progression-free survival (PFS) was 7.1 and 3.1 months in the low-BNML and high-BNML groups, respectively (p = 0.010). The median PFS was 9.1 and 3.5 months in the low-BSLD and high-BSLD groups, respectively (p = 0.004). Moreover, patients with high SUVmax levels had worse overall survival (OS) and PFS. BNML, BSLD, and SUVmax are useful prognostic factors in patients with RM-HNC treated with ICIs. Imaging examinations before ICI treatment are recommended to predict the efficacy of ICIs. If the tumor burden is high, cytotoxic anticancer agents may be administered concomitantly with or prior to ICI monotherapy., (© 2022. The Author(s).)
- Published
- 2022
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