Peritumoral Lymphatic Vessels Associated with Resistance to Neoadjuvant Chemotherapy and Unfavorable Survival in Esophag
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ORIGINAL ARTICLE – HEALTH SERVICES RESEARCH AND GLOBAL ONCOLOGY
Peritumoral Lymphatic Vessels Associated with Resistance to Neoadjuvant Chemotherapy and Unfavorable Survival in Esophageal Cancer Takeo Hara, MD, PhD1, Tomoki Makino, MD, PhD1, Makoto Yamasaki, MD, PhD1, Koji Tanaka, MD, PhD1, Kotaro Yamashita, MD, PhD1, Yuya Nogi, MD1, Takuro Saito, MD, PhD1, Tsuyoshi Takahashi, MD, PhD1, Yukinori Kurokawa, MD, PhD1, Mitsuaki Tatsumi, MD, PhD2, Kiyokazu Nakajima, MD, PhD1, Eiichi Morii, MD, PhD3, Hidetoshi Eguchi, MD, PhD1, and Yuichiro Doki, MD, PhD1 1
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; 3Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan 2
ABSTRACT Background. Peri- or intra-tumor lymphangiogenesis is induced in several types of cancer. However, the significance of peritumoral lymphatic vessels (LVs) in esophageal cancer (EC) remains to be clarified. Methods. This study included 162 eligible EC patients with or without neoadjuvant chemotherapy (NAC). The numbers of non-tumoral and peritumoral LVs were counted in resected specimens based on podoplanin immunostaining. The association between peritumoral LV number and clinicopathologic parameters, including tumor heterogeneity as measured by positron emission tomography, NAC response, and patient survival were analyzed. Results. In non-NAC patients, the number of peritumoral LVs was highest in the lamina propria mucosa (LPM), followed by non-tumoral LVs in the LPM, peritumoral LVs in the submucosa (SM), and non-tumoral LVs in the SM. The patients with a low number of peritumoral LVs in the LPM versus those with a high number constituted a larger fraction of the NAC patients (67.8% vs. 50.0%; P = 0.022)
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-08474-x) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2020 First Received: 22 December 2019 T. Makino, MD, PhD e-mail: [email protected]
and had a poorer pathologic response to NAC (grades 0–1a: 68.8% vs. 47.2%; P = 0.035), as well as greater tumor heterogeneity and worse survival (5-year overall survival: 50.6% vs. 72.8%; P = 0.0097). The number of peritumoral LVs in the LPM was identified as an independent prognostic factor with the highest hazard ratio (HR) of overall survival (HR 2.06; P = 0.0049) in the multivariate analysis. Conclusion. For EC patients, peritumoral LVs in the LPM layer are associated with tumor heterogeneity, response to NAC, and unfavorable survival.
Esophageal cancer (EC) is associated with a poor prognosis due to the relatively high risk of lymphatic metastasis, even in early stages.1 Although neoadjuvant chemotherapy (NAC) followed by surgery has become the standard therapy based on a recent phase 3 trial,2,3 nonresponders to NAC
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