Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008

Hidetoshi Shimizu; Takeshi Kodaira; Naomi Kiyota; Ryuichi Hayashi; Hiroshi Nishino; Yukinori Asada; Hiroki Mitani; Yuuji Hirayama; Yusuke Onozawa; Naoki Nishio; Nobuhiro Hanai; Akira Ohkoshi; Hiroki Hara; Nobuya Monden; Masato Nagaoka; Shujiro Minami; Takashi Fujii; Kaoru Tanaka; Akihiro Homma; Seiichi Yoshimoto; Nobuhiko Oridate; Koichi Omori; Tsutomu Ueda; Kenji Okami; Hirokazu Uemura; Kiyoto Shiga; Mitsuhiko Nakahira; Takahiro Asakage; Yuki Saito; Keita Sasaki; Ryo Kitabayashi; Satoshi Ishikura; Yasumasa Nishimura; Makoto Tahara

doi:10.1016/j.oraloncology.2024.106976

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008

Oral Oncol. 2024 Oct:157:106976. doi: 10.1016/j.oraloncology.2024.106976. Epub 2024 Aug 6.

Authors

Hidetoshi Shimizu¹, Takeshi Kodaira², Naomi Kiyota³, Ryuichi Hayashi⁴, Hiroshi Nishino⁵, Yukinori Asada⁶, Hiroki Mitani⁷, Yuuji Hirayama⁸, Yusuke Onozawa⁹, Naoki Nishio¹⁰, Nobuhiro Hanai¹¹, Akira Ohkoshi¹², Hiroki Hara¹³, Nobuya Monden¹⁴, Masato Nagaoka¹⁵, Shujiro Minami¹⁶, Takashi Fujii¹⁷, Kaoru Tanaka¹⁸, Akihiro Homma¹⁹, Seiichi Yoshimoto²⁰, Nobuhiko Oridate²¹, Koichi Omori²², Tsutomu Ueda²³, Kenji Okami²⁴, Hirokazu Uemura²⁵, Kiyoto Shiga²⁶, Mitsuhiko Nakahira²⁷, Takahiro Asakage²⁸, Yuki Saito²⁹, Keita Sasaki³⁰, Ryo Kitabayashi³¹, Satoshi Ishikura³², Yasumasa Nishimura³³, Makoto Tahara³⁴

Affiliations

¹ Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: [email protected].
² Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: [email protected].
³ Department of Medical Oncology and Hematology, Kobe University Hospital, Cancer Center, Kobe, Japan. Electronic address: [email protected].
⁴ Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: [email protected].
⁵ Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University Hospital, Shimotsuke, Japan. Electronic address: [email protected].
⁶ Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan. Electronic address: [email protected].
⁷ Department of Head and Neck Oncology, Cancer Institute Hospital, Tokyo, Japan. Electronic address: [email protected].
⁸ Department of Head and Neck Surgery, Hyogo Cancer Center, Akashi, Japan. Electronic address: [email protected].
⁹ Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: [email protected].
¹⁰ Department of Otorhinolaryngology, Nagoya University Hospital, Nagoya, Japan. Electronic address: [email protected].
¹¹ Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: [email protected].
¹² Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital, Sendai, Japan. Electronic address: [email protected].
¹³ Department of Gastroenterology, Saitama Cancer Center, Ina, Japan. Electronic address: [email protected].
¹⁴ Department of Head and Neck Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. Electronic address: [email protected].
¹⁵ Department of Otolaryngology, Jikei University School of Medicine, Tokyo, Japan. Electronic address: [email protected].
¹⁶ Department of Otolaryngology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Electronic address: [email protected].
¹⁷ Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Japan. Electronic address: [email protected].
¹⁸ Department of Medical Oncology, Kindai University Hospital, Osakasayama, Japan. Electronic address: [email protected].
¹⁹ Department of Otolaryngology - Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan. Electronic address: [email protected].
²⁰ Department of Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan. Electronic address: [email protected].
²¹ Department of Otolaryngology - Head and Neck Surgery, Yokohama City University Hospital, Yokohama, Japan. Electronic address: [email protected].
²² Department of Otolaryngology - Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: [email protected].
²³ Department of Otorhinolaryngology, Head and Neck Surgery, Hiroshima University Hospital, Hiroshima, Japan. Electronic address: [email protected].
²⁴ Department of Otolaryngology, Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan. Electronic address: [email protected].
²⁵ Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Japan. Electronic address: [email protected].
²⁶ Department of Head and Neck Surgery, Iwate Medical University Hospital, Iwate, Japan. Electronic address: [email protected].
²⁷ Department of Head and Neck Surgery, Otolaryngology, Saitama Medical University International Medical Center, Hidaka, Japan. Electronic address: [email protected].
²⁸ Department of Head and Neck Surgery, Tokyo Medical and Dental University Hospital, Tokyo, Japan. Electronic address: [email protected].
²⁹ Department of Otolaryngology, Head and Neck Surgery, The University of Tokyo, Tokyo, Japan. Electronic address: [email protected].
³⁰ Japan Clinical Oncology Group Data Center/Operations office, National Cancer Center Hospital, Tokyo, Japan. Electronic address: [email protected].
³¹ Japan Clinical Oncology Group Data Center/Operations office, National Cancer Center Hospital, Tokyo, Japan. Electronic address: [email protected].
³² Department of Radiation Oncology, St. Luke's International Hospital, St. Luke's International University, Tokyo, Japan. Electronic address: [email protected].
³³ Professor Emeritus, Kindai University, Osakasayama, Japan. Electronic address: [email protected].
³⁴ Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan. Electronic address: [email protected].

PMID: 39111143
DOI: 10.1016/j.oraloncology.2024.106976

Abstract

Background and purpose: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data.

Materials and methods: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism.

Results: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V_60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism.

Conclusion: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Keywords: Hypothyroidism; Intensity modulated radiation therapy; JCOG1008; Randomized controlled trial; Secondary analysis; Weekly cisplatin; high-risk postoperative head and neck cancer (HNC).

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Chemoradiotherapy / adverse effects
Female
Head and Neck Neoplasms* / radiotherapy
Head and Neck Neoplasms* / therapy
Humans
Hypothyroidism* / epidemiology
Hypothyroidism* / etiology
Incidence
Male
Middle Aged
Risk Factors